Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both...Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5' and 3' flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the data in the literature on the genetic association between the -174 G/C polymorphism and some specific liver diseases characterized by different etiologies are still controversial. In particular, most of the studies are quite unanimous in describing a correlation between the presence of the high-producer genotype and a worse evolution of the chronic liver disease. This is valid for patients with hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis and hepatocellu-lar carcinoma (HCC) whatever the etiology. Studies in hepatitis B virus-related chronic liver diseases are not conclusive, while specific populations like non alcoholic fatty liver disease/non-alcoholic steatohepatitis, autoimmune and human immunodeficiency virus/HCV coinfected patients show a higher prevalence of the lowproducer genotype, probably due to the complexity of these clinical pictures. In this direction, a systematic revision of these data should shed more light on the role of this polymorphism in chronic liver diseases and HCC.展开更多
AIM： To study the therapeutic effect of exogenous interleuldn-10 on CCl4-induced hepatic fibrosis in rats and its passible mechanisms. METHODS： Fourty-seven SD rats were randomly divided into control group （group N...AIM： To study the therapeutic effect of exogenous interleuldn-10 on CCl4-induced hepatic fibrosis in rats and its passible mechanisms. METHODS： Fourty-seven SD rats were randomly divided into control group （group N） and CCl4-induced hepatic fibrosis model group （group C）. After CCl4 was given for 9 wk, the model group was divided into three groups. Rats in group H were put to death immediately, rats in group T were treated with IL-10 for another three wk and then put to death, rats in group R recovered after three weeks and were then killed. The degree of hepatic fibrosis was measured by HE staining and histological activity index （HAI）. Histological activity index （HAI）, change of collagen types Ⅰ and Ⅲ were measured by Picrosirius staining. The expression of TNF-α, HHP-2 and TIMP-1 in liver tissue was measured by S-P immunohis tochemistry.RESULTS： CCl4- induced experimental rat hepatic fibrosis model was established successfully. The degree of hepatic fibrosis was markedly lower in group T than in groups H and R, and there was no difference between the two groups. The expression of collagen types I and III was significantly suppressed in group T and was slightly suppressed in groups H and R. The positive levels of TNF-α, HHP-2 and TIHP-1 in group H increased significantly compared to those in group N （P〈0.01）. The positive signals decreased significantly in groups T and R （P〈0.01）, but positive score was significantly lower in group T than in group R （P〈 0.01）. CONCLUS10N： Exogenous IL-10 can reverse CCl4-induced hepatic fibrosis in rats. IL-10 may exert its reversible effects on hepatic fibrosis by blocking CCl4-induced inflammation, inhibiting expression of HHP-2 and TIMP-1 and promoting resolution of collagen types Ⅰ and Ⅲ.展开更多
AIM： To study the relationship between interleukin-lbeta （IL-1β） up-regulating tissue inhibitor of matrix metalloproteinase-1 （TIMMP-1） mRNA expression and phosphorylation of both c-jun N-terminal kinase （INK）...AIM： To study the relationship between interleukin-lbeta （IL-1β） up-regulating tissue inhibitor of matrix metalloproteinase-1 （TIMMP-1） mRNA expression and phosphorylation of both c-jun N-terminal kinase （INK） and p38 in rat heffatic stellate cells （HSC）. METHODS： RT-PCR was performed to measure the expression of TIMMP-1 mRNA in rat HSC. Western blot was performed to measure IL-1β-induced JNK and p38 activities in rat HSC. RESULTS： TIMMP-1 mRNA expression （1.191± 0.079） was much higher after treatment with IL-1β （10 ng/mL） for 24 h than in control group （0.545±0.091） （P〈0.01）. IL-1β activated INK and p38 in a time-dependent manner. After stimulation with IL-1β for 0, 5, 15, 30, 60 and 120 min, the INK activity was 0.982±0.299, 1.501±0.720, 2.133±0.882, 3.360±0.452, 2.181±0.789, and 1.385 ± 0.368, respectively. There was a significant difference in JNK activity at 15 min （P〈 0.01）, 30 min （P〈 0.01） and 60 min （P〈0.01） in comparison to that at 0 min. The p38 activity was 1.061±0.310, 2.050±0.863, 2.380±0.573, 2.973±0.953, 2.421±0.793, and 1.755 ± 0.433 at the 6 time points （0, 5, 15, 30, 60 and 120 min） respectively. There was a significant difference in p38 activity at 5 min （P〈0.05）, 15 min （P〈0.01）, 30 min （P〈0.01） and 60 min （P〈0.01） compared to that at 0 min. TIMMP-1 mRNA expression trended to decrease in 3 groups pretreated with different concentrations of SP600125 （10 μmol/L, 1.022±0.113; 20 μmol/L, 0.869±0.070; 40 μmol/L, 0.666±0.123）. Their decreases were all significant （P〈0.05, P〈0.01, P〈0.01） in comparison to control group （without SP600125 treatment, 1.163±0.107）. In the other 3 groups pretreated with different concentrations of SB203580 （10 μmol/L, 1.507±0.099; 20 μmol/L, 1.698±0.107; 40 μmol/L, 1.857±0.054）, the expression of TIMMP-1 mRNA increased. Their levels were higher than those in the control group （without SB203580 treatment, 1.027 ± 0.061） with a significant statistical significance （P〈 0.01）. CONCLUSION： IL-1β has a direct action on hepatic fibrosis by up-regulating TIMMP-1 mRNA expression in ratessionin in rate HSC.JNK and p38 mitogen-activated protein kinases （MAPKs） are involved in IL-1β-induced TIMMP-1 gene expression, and play a distinct role in this process, indicating that p38 and .INK pathways cooperatively mediate TIMP-1 mRNA expression in rat HSC.展开更多
Objective: To investigate the synergistic anti-tumor effects of murine IL-12 gene and HSV-TK gene therapy in mice bearing liver cancer. Methods: Mouse liver cancer MM45T. Li (H-2d) cells were transfected with retrovi...Objective: To investigate the synergistic anti-tumor effects of murine IL-12 gene and HSV-TK gene therapy in mice bearing liver cancer. Methods: Mouse liver cancer MM45T. Li (H-2d) cells were transfected with retroviral vector containing IL-12 gene or HSV-TK gene insert. Gene-modified liver cancer cells, MM45T. Li/IL-12 and MM45T. Li/TK, with stable expression of IL-12 and TK were obtained. Balb/c mice were inoculated subcutaneously with 2′105 MM45T. Li cells. When the tumor reached a size of 0.5-1.0 cm, a mixture of MM45T.Li/TK cells and 60Co-irradiated MM45T. Li/IL-12 cell were injected intratumoraly. Ganciclovir (GCV) was injected ip (40 mg.kg-1.d-1) for 10 days. Intratumoral injection of 60Co-irradiated MM45T. Li/IL-12 cells was repeated twice in one week apart. Mice with distant tumors were treated according to the same protocol. CTL activity of spleen cells was measured by 51Cr-release assay and phenotype of tumor infiltrating lymphocytes by immunohistochemical staining. Results: In mice treated with MM45T. Li/IL-12 or MM45T. Li/TK+GCV individually led to moderate reduction in tumor growth, but neither could eradicate the tumor completely, while in 60% of mice treated with a mixture of MM45T. Li/IL-12 and MM45T. Li/TK cells plus GCV, complete tumor regression was observed, with no tumor recurrence for two months. The growth of distant tumor was also inhibited significantly in mice similarly treated. Most of the mice received combined gene therapy plus GCV had abundant CD4+, CD8+T lymphocyte infiltration. Their CTL activity was significantly higher than in mice received single gene therapy. Conclusion Combination therapy with IL-12 gene and HSV-TK gene plus GCV is effective for mouse liver cancer.展开更多
AIM: To compare the influence of different transplant sites in bone marrow mesenchymal stem cell (MSC)-based therapy for liver fibrosis. METHODS: MSCs isolated from Sprague Dawley (SD) rats were induced into hepatocyt...AIM: To compare the influence of different transplant sites in bone marrow mesenchymal stem cell (MSC)-based therapy for liver fibrosis. METHODS: MSCs isolated from Sprague Dawley (SD) rats were induced into hepatocyte-like cells. Liver fibrosis in SD rats was induced with carbon tetrachloride. Following hepatocyte induction in vitro, 4',6-diamidino- 2-phenylindole (DAPI)-labeled MSCs were transplanted by intravenous, intrahepatic, and intraperitoneal injection. Histopathological staining, immunohistochemistry, and biochemical analysis were used to compare the morphological and functional liver regeneration among different MSC injection modalities. The expression differences of interleukins, growth factor, extracellular matrix, matrix metalloproteinases, and tissue inhibitor of metalloproteinase were examined by real-time reverse transcription-polymerase chain reaction (RT-PCR) andenzyme linked immunosorbent assay (ELISA). RESULTS: Four days after exposure to hepatocyte differentiation medium, MSCs that did not express hepatocyte markers could express α-fetoprotein, albumin, and cytokeratin 18. The results of histopathological staining, immunohistochemistry, and biochemical analysis indicated that intravenous injection is more effective at rescuing liver failure than other injection modalities. DAPI-labeled cells were found around liver lobules in all three injection site groups, but the intravenous group had the highest number of cells. PCR and ELISA analysis indicated that interleukin-10 (IL-10) was highest in the intravenous group, whereas il1β, il6, tnfα and tgfβ, which can be regulated by IL10 and are promoters of liver fibrosis, were significantly lower than in the other groups. CONCLUSION: MSC administration is able to protect against liver fibrosis. Intravenous injection is the most favorable treatment modality through promotion of IL10 expression.展开更多
Conventional adaptive T cell responses contribute to liver inflammation and fibrogenesis,especially in chronic viral infections and autoimmune hepatitis.However,the role of unconventional gamma-delta(γδ)T cells in l...Conventional adaptive T cell responses contribute to liver inflammation and fibrogenesis,especially in chronic viral infections and autoimmune hepatitis.However,the role of unconventional gamma-delta(γδ)T cells in liver diseases is less clear.In the past two decades,accumulating evidence revealed thatγδT cell numbers remarkably increase in the liver upon various inflammatory conditions in mice and humans.More recent studies demonstrated that the functional effect ofγδT cells on liver disease progression depends on the subsets involved,which can be identified by the expression of distinct T cell receptor chains and of specific cytokines.Fascinatingly,γδT cells may have protective as well as pathogenic functions in liver diseases.Interferonγ-producingγδT cells,for example,induce apoptosis in hepatocytes but also in hepatic tumor cells;while interleukin-17-expressingγδT cells can downregulate pathogenic effector functions of other immune cells and can promote apoptosis of fibrogenic stellate cells.However,the results obtained in human liver disease as well as murine models are not fully conclusive at present,and the effects ofγδT cells on the outcome of liver disease might vary dependent on etiology and stage of disease.Further definitions of theγδT cell subsets in-volved in acute and chronic liver inflammation,as well as their effector cytokines might uncover whether interference withγδT cells could be a useful target for the treatment of liver disease.展开更多
AIM: To identify the property of dendritic cells (DCs) of peripheral blood monocytes (PBMC) in patients with chronic HBV infection. METHODS: Twenty patients with persistent HBV infection were included in this study, 1...AIM: To identify the property of dendritic cells (DCs) of peripheral blood monocytes (PBMC) in patients with chronic HBV infection. METHODS: Twenty patients with persistent HBV infection were included in this study, 10 healthy subjects being used as a control group. The peripheral blood mononuclear cells (PBMC) of T cell-depleted populations were incubated and induced into mature dendritic cells in the RPMI-1640 medium in the presence of cytokines GM-CSF, IL-4, FLt-3,TNF-alpha and 100mL.L(-1 )of fetal calf serum for a total of 10-12 days. The expressions of surface markers on DCs were evaluated using flow cytometric analysis. ELISA method was used to determine the cytokine levels of interleukin-12 (IL-12) and IL-10 in the supernatant produced by DCs. For detection of the stimulatory capacity of DCs to T cell proliferation, mytomycin C-treated DC were incubated with allogenic T cells. RESULTS: A typical morphology of mature DCs from healthy subjects and HBV-infected patients was induced in in vitro incubation, but the proliferation ability and cellular number of DCs from HBV-infected patients significantly decreased compared with healthy individuals. In particular, the expression levels of HLA-DR, CD80 (B7-1) and CD86 (B7-2) on DC surface from patients were also lower than that from healthy individuals (0.46 vs 0.92 for HLA-DR, 0.44 vs 0.88 for CD80 and 0.44 vs 0.84 for CD86,P【0.05). The stimulatory capacity and production of IL-12 of DCs from patients in allogenic mixed lymphocyte reaction (AMLR) significantly decreased, but the production level of nitric oxide (NO) by DCs simultaneously increased compared with healthy subjects (86 +/- 15 vs 170 +/- 22 micromol.L(-1), P 【0.05). CONCLUSION: The patients with chronic HBV infection have the defective function and immature phenotype of dendritic cells, which may be associated with the inability of efficient presentation of HBV antigens to host immune system for the clearance of HBV.展开更多
AIM:Cytokine release by macrophages critically determines the type of immune response to an antigen.Therefore,we studied hepatitis C virus(HCV)-specific induction of interleukins-1β,-10,-12(IL-1β,IL-10,IL-12),and tu...AIM:Cytokine release by macrophages critically determines the type of immune response to an antigen.Therefore,we studied hepatitis C virus(HCV)-specific induction of interleukins-1β,-10,-12(IL-1β,IL-10,IL-12),and tumor necrosis factor-α(TNF-α)in monocytes. METHODS:Intracallular cytokine expression was studied by flow cytometry in 23 patients with chronic hepatitis C,14 anti-HCV seropositives without viremia and 11 controls after stimulation of peripheral blood mononuclear calls with recombinant core,NS3,NS4,NSSa and NSSb proteins. RESULTS:Patients with HCV viremia revealed greater spontaneous expression of IL-1β,TNF-α,and IL-10. Furthermore,greater than twofold higher IL-10 expression was induced by the HCV antigens in chronic hepatitis C than in the other two groups(P<0.05).In contrast,neither IL- 12 nor TNF-α was induced preferentially. CONCLUSION:In chronic hepatitis C antigen-specific cytokine induction in monocytes is apparently shifted towards predominant IL-10 induction-not counterbalanced by antiviral type 1 cytokines.This may contribute to persistent viral replication.展开更多
AIM: To assess vitamin D in hepatitis C patients and its relationship to interleukin (IL)-23, IL-17, and macrophage chemoattractant protein-1 (MCP-1). METHODS: The study was conducted on 50 Egyptian hepatitis C virus ...AIM: To assess vitamin D in hepatitis C patients and its relationship to interleukin (IL)-23, IL-17, and macrophage chemoattractant protein-1 (MCP-1). METHODS: The study was conducted on 50 Egyptian hepatitis C virus (HCV) genotype number IV-infected patients and 25 age- and gender-matched healthy subjects. Venous blood samples were obtained. Samples were allowed to clot and sera were separated by centrifugation and stored at -20?°C. A 25 hydroxy vitamin D assay was carried out using solid phase RIA. A 1,25 dihydroxy vitamin D assay was carried out using a commercial kit purchased from Incstar Corporation. IL-17 and -23 and MCP-1 were assayed by an enzyme immunoassay. Quantitative and qualitative polymerase chain reaction for HCV virus were done by TaqMan technology. Only HCV genotype IV-infected subjects were included in the study. The mean ± SD were determined, a t-test for comparison of means of different parameters was used. Correlation analysis was done using Pearson’s correlation. Differences among different groups were determined using the Kruskal-Wallis test. RESULTS: The mean vitamin D level in HCV patients (group?I) was 15 ± 5.2 ng/mL while in control (group II) was 39.7 ± 10.8. For active vitamin D in group?I?as 16.6 ± 4.8 ng/mL while in group II was 41.9 ± 7.9. IL-23 was 154 ± 97.8 in group?I?and 6.7 ± 2.17 in group II. IL-17 was 70.7 ± 72.5 in cases and 1.2 ± 0.4 in control. MCP-1 was 1582 ± 794.4 in group?I?and 216.1 ± 5.38 in group II. Vitamin D deficiency affected 72% of HCV-infected patients and 0% of the control group. Vitamin D insufficiency existed in 28% of HCV-infected patients and 12% of the control group. One hundred percent of the cirrhotic patients and 40% of non cirrhotic HCV-infected patients had vitamin D deficiency. IL-23, IL-17, and MCP-1 were markedly increased in HCV-infected patients in comparison to controls.A significant negative correlation between vitamin D and IL-17 and -23 and MCP-1 was detected. HCV-infected males and females showed no differences with respect to viral load, vitamin D levels, IL-17, IL-23 and MCP-1. The viral load was negatively correlated with vitamin D and active vitamin D (P = 0.0001 and P = 0.001, respectively), while positively correlated with IL-23, IL-17, and MCP-1. We classified the patients according to sonar findings into four groups. Group?Ia with bright hepatomegaly and included 14 patients. Group?Ib with perihepatic fibrosis and included 11 patients. Group?Ic with liver cirrhosis and included 11 patients. Group?Id with hepatocellular carcinoma (HCC) and included 14 patients. Vitamin D and active vitamin D were shown to be lower in cirrhotic patients and much lower in patients with HCC, and this difference was highly significant (P = 0.0001). IL-17 and -23 and MCP-1 were higher in advanced liver disease) and the differences were highly significant (P = 0.0001). CONCLUSION: Whether the deficiency of vitamin D is related to HCV-induced chronic liver disease or predisposing factor for higher viral load is a matter of debate.展开更多
AIM: To investigate the association of the functional monocyte chemotactic protein-1 (MCP-1) promoter polymorphism (A-2518G) with spontaneous bacterial peritonitis (SBP).
OBJECTIVE:To investigate the mechanism by which Daifan San(DFS)prevents and treats primary biliary cirrhosis(PBC)via the forkhead box P3(FoxP3)and interleukin(IL)-23/IL-17A signaling pathways.METHODS:Ninety C57BL/6 mi...OBJECTIVE:To investigate the mechanism by which Daifan San(DFS)prevents and treats primary biliary cirrhosis(PBC)via the forkhead box P3(FoxP3)and interleukin(IL)-23/IL-17A signaling pathways.METHODS:Ninety C57BL/6 mice were randomly divided into the control,model,DFS low-dose,DFS middle-dose,DFS high-dose and ursodeoxycholic acid(UDCA)groups(n=15 per group).A mouse model of PBC was induced using polyinosinic polycytidylic acids(poly I:C).Lymphocyte subset expression in the peripheral blood was analyzed via flow cytometry.The inflammatory cytokines and antimitochondrial autoantibody(AMA)levels were detected via enzyme-linked immunosorbent assays.The expressions and location of typeⅠcollagen,typeⅢcollagen,cytokeratin 19 and FoxP3 in the liver tissue were evaluated via immunohistochemistry.FoxP3,IL-23 and IL-17 expressions in the peripheral blood and liver tissue were evaluated via real-time polymerase chain reaction and western blotting.RESULTS:IL-17,IL-23,IL-8,IL-33,TNF-α,and AMA expressions were significantly increased in the model group and decreased in the DFS and UDCA groups.Conversely,Treg cell and FoxP3 expressions were significantly decreased in the model group and increased in the DFS and UDCA groups.The IL-23/IL-17A signaling pathway was closely correlated with chronic inflammation of the bile duct in PBC and functional deletion of Treg cells,leading to reduced FoxP3 levels and mediating the loss of tolerance in PBC.CONCLUSION:DFS may delay the occurrence and relieve the symptoms of PBC by downregulating IL-23/IL-17A signaling pathway expression and upregulating FoxP3 expression.展开更多
Myeloid derived suppressor cells(MDSC) are a heterogeneous population of immune cells that are potent suppressors of immune responses. MDSC emerge in various compartments in the body, such as blood, bonemarrow or sple...Myeloid derived suppressor cells(MDSC) are a heterogeneous population of immune cells that are potent suppressors of immune responses. MDSC emerge in various compartments in the body, such as blood, bonemarrow or spleen, especially in conditions of cancer, infections or inflammation. MDSC usually express CD11 b, CD33, and low levels of human leukocyte antigen-DR in humans or CD11 b and Gr1(Ly6C/G) in mice, and they can be further divided into granulocytic or monocytic MDSC. The liver is an important organ for MDSC induction and accumulation in hepatic as well as extrahepatic diseases. Different hepatic cells, especially hepatic stellate cells, as well as liver-derived soluble factors, including hepatocyte growth factor and acute phase proteins(SAA, KC), can promote the differentiation of MDSC from myeloid cells. Importantly, hepatic myeloid cells like neutrophils, monocytes and macrophages fulfill essential roles in acute and chronic liver diseases. Recent data from patients with liver diseases and animal models linked MDSC to the pathogenesis of hepatic inflammation, fibrosis and hepatocellular carcinoma(HCC). In settings of acute hepatitis, MDSC can limit immunogenic T cell responses and subsequent tissue injury. In patients with chronic hepatitis C, MDSC increase and may favor viral persistence. Animal models of chronic liver injury, however, have not yet conclusively clarified the involvement of MDSC for hepatic fibrosis. In human HCC and mouse models of liver cancer, MDSC are induced in the tumor environment and suppress anti-tumoral immune responses. Thus, the liver is a primary site of MDSC in vivo, and modulating MDSC functionality might represent a promising novel therapeutic target for liver diseases.展开更多
Sepsis-induced liver injury(SILI)is an important cause of septicemia deaths.BaWeiBaiDuSan(BWBDS)was extracted from a formula of Panax ginseng C.A.Meyer,Lilium brownie F.E.Brown ex Miellez var.viridulum Baker,Polygonat...Sepsis-induced liver injury(SILI)is an important cause of septicemia deaths.BaWeiBaiDuSan(BWBDS)was extracted from a formula of Panax ginseng C.A.Meyer,Lilium brownie F.E.Brown ex Miellez var.viridulum Baker,Polygonatum sibiricum Delar.ex Redoute,Lonicera japonica Thunb.,Hippophae rhamnoides Linn.,Amygdalus Communis Vas,Platycodon grandiflorus(Jacq.)A.DC.,and Cortex Phelloderdri.Herein,we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota.BWBDS protected mice against SILI,which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity.BWBDS selectively promoted the growth of Lactobacillus johnsonii(L.johnsonii)in cecal ligation and puncture treated mice.Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects.Notably,L.johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity,increasing interleukin-10+M2 macrophage production and enhancing intestinal integrity.Furthermore,heat inactivation L.johnsonii(HI-L.johnsonii)treatment promoted macrophage anti-inflammatory activity and alleviated SILI.Our findings revealed BWBDS and gut microbiota L.johnsonii as novel prebiotic and probiotic that may be used to treat SILI.The potential underlying mechanism was at least in part,via L.johnsonii-dependent immune regulation and interleukin-10+M2 macrophage production.展开更多
Reactive arthritis （ReA）, also known as sterile postin-fectious arthritis, belongs to the group of related ar-thropathies known as spondyloarthritis （SpA）. ReA can arise 1-4 wk after a gastrointestinal or genitour...Reactive arthritis （ReA）, also known as sterile postin-fectious arthritis, belongs to the group of related ar-thropathies known as spondyloarthritis （SpA）. ReA can arise 1-4 wk after a gastrointestinal or genitourinary infection, but once arthritis develops, the microorgan-ism is not found in the joint. The classical microbes as-sociated with ReA development include Gram-negative aerobic or microaerophilic bacteria containing LPS in their outer membrane. The immunopathogenic mechanisms involved in ReA development are still unknown. A hypothesis suggested that the bacteria probably persist outside the joint, at sites such as gut mucosa or lymph nodes, and bacterial antigens might then be transported to the joints. On the other hand, an altered immune response and the unbalanced production of cy-tokines have been reported in subjects with ReA. Currently, there is increased evidence to suggest that both mechanisms would operate in the immunopathogenesis of ReA. In this review we highlight recent advances on the role of cytokines in the ReA. Particularly, we discuss the roles of some pro- and anti-infammatory cytokines involved in the immunopathogenesis of ReA.展开更多
Available reports suggest that, Leishmania donovani antigen KMP-11 may be significant in the modulation of immune responses in visceral leishmaniasis (VL). This study evaluated vaccine prospect of presentation of KMP-...Available reports suggest that, Leishmania donovani antigen KMP-11 may be significant in the modulation of immune responses in visceral leishmaniasis (VL). This study evaluated vaccine prospect of presentation of KMP-11 antigen through murine dendritic cells against VL in infected BALB/c mice. We report here that immunization with KMP-11 delivered through bone marrow derived dendritic cells can lead to killing of L. donovani in infected BALB/c mice. Furthermore, the strategy to use KMP-11 as vaccine delivered through DCs can stimulate the production of IFN-g, IL-12, IL-2R and TNF-α with concomitant down-regulation of IL-10 and IL-4. Furthermore, anti-leishmanial defence function (ROS) of splenocytes was observed increased in the presence of DC-delivered KMP-11 vaccination accompanied with an increased p38-MAPK signalling in vaccinated splenocytes. We summarized from our data that KMP-11 delivered through DCs has potential for eliciting protective immunity through pro-inflammatory cytokines (IFN-γ, IL-12, IL-2, TNF-α) following an up-regulation in signalling event of p38-MAPK. Therefore the study suggests a new control strategy against VL in future.展开更多
文摘Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5' and 3' flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the data in the literature on the genetic association between the -174 G/C polymorphism and some specific liver diseases characterized by different etiologies are still controversial. In particular, most of the studies are quite unanimous in describing a correlation between the presence of the high-producer genotype and a worse evolution of the chronic liver disease. This is valid for patients with hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis and hepatocellu-lar carcinoma (HCC) whatever the etiology. Studies in hepatitis B virus-related chronic liver diseases are not conclusive, while specific populations like non alcoholic fatty liver disease/non-alcoholic steatohepatitis, autoimmune and human immunodeficiency virus/HCV coinfected patients show a higher prevalence of the lowproducer genotype, probably due to the complexity of these clinical pictures. In this direction, a systematic revision of these data should shed more light on the role of this polymorphism in chronic liver diseases and HCC.
基金Supported by Nature Science Foundation of Fujian Province. No.2005D094 and No.C0410025
文摘AIM： To study the therapeutic effect of exogenous interleuldn-10 on CCl4-induced hepatic fibrosis in rats and its passible mechanisms. METHODS： Fourty-seven SD rats were randomly divided into control group （group N） and CCl4-induced hepatic fibrosis model group （group C）. After CCl4 was given for 9 wk, the model group was divided into three groups. Rats in group H were put to death immediately, rats in group T were treated with IL-10 for another three wk and then put to death, rats in group R recovered after three weeks and were then killed. The degree of hepatic fibrosis was measured by HE staining and histological activity index （HAI）. Histological activity index （HAI）, change of collagen types Ⅰ and Ⅲ were measured by Picrosirius staining. The expression of TNF-α, HHP-2 and TIMP-1 in liver tissue was measured by S-P immunohis tochemistry.RESULTS： CCl4- induced experimental rat hepatic fibrosis model was established successfully. The degree of hepatic fibrosis was markedly lower in group T than in groups H and R, and there was no difference between the two groups. The expression of collagen types I and III was significantly suppressed in group T and was slightly suppressed in groups H and R. The positive levels of TNF-α, HHP-2 and TIHP-1 in group H increased significantly compared to those in group N （P〈0.01）. The positive signals decreased significantly in groups T and R （P〈0.01）, but positive score was significantly lower in group T than in group R （P〈 0.01）. CONCLUS10N： Exogenous IL-10 can reverse CCl4-induced hepatic fibrosis in rats. IL-10 may exert its reversible effects on hepatic fibrosis by blocking CCl4-induced inflammation, inhibiting expression of HHP-2 and TIMP-1 and promoting resolution of collagen types Ⅰ and Ⅲ.
文摘AIM： To study the relationship between interleukin-lbeta （IL-1β） up-regulating tissue inhibitor of matrix metalloproteinase-1 （TIMMP-1） mRNA expression and phosphorylation of both c-jun N-terminal kinase （INK） and p38 in rat heffatic stellate cells （HSC）. METHODS： RT-PCR was performed to measure the expression of TIMMP-1 mRNA in rat HSC. Western blot was performed to measure IL-1β-induced JNK and p38 activities in rat HSC. RESULTS： TIMMP-1 mRNA expression （1.191± 0.079） was much higher after treatment with IL-1β （10 ng/mL） for 24 h than in control group （0.545±0.091） （P〈0.01）. IL-1β activated INK and p38 in a time-dependent manner. After stimulation with IL-1β for 0, 5, 15, 30, 60 and 120 min, the INK activity was 0.982±0.299, 1.501±0.720, 2.133±0.882, 3.360±0.452, 2.181±0.789, and 1.385 ± 0.368, respectively. There was a significant difference in JNK activity at 15 min （P〈 0.01）, 30 min （P〈 0.01） and 60 min （P〈0.01） in comparison to that at 0 min. The p38 activity was 1.061±0.310, 2.050±0.863, 2.380±0.573, 2.973±0.953, 2.421±0.793, and 1.755 ± 0.433 at the 6 time points （0, 5, 15, 30, 60 and 120 min） respectively. There was a significant difference in p38 activity at 5 min （P〈0.05）, 15 min （P〈0.01）, 30 min （P〈0.01） and 60 min （P〈0.01） compared to that at 0 min. TIMMP-1 mRNA expression trended to decrease in 3 groups pretreated with different concentrations of SP600125 （10 μmol/L, 1.022±0.113; 20 μmol/L, 0.869±0.070; 40 μmol/L, 0.666±0.123）. Their decreases were all significant （P〈0.05, P〈0.01, P〈0.01） in comparison to control group （without SP600125 treatment, 1.163±0.107）. In the other 3 groups pretreated with different concentrations of SB203580 （10 μmol/L, 1.507±0.099; 20 μmol/L, 1.698±0.107; 40 μmol/L, 1.857±0.054）, the expression of TIMMP-1 mRNA increased. Their levels were higher than those in the control group （without SB203580 treatment, 1.027 ± 0.061） with a significant statistical significance （P〈 0.01）. CONCLUSION： IL-1β has a direct action on hepatic fibrosis by up-regulating TIMMP-1 mRNA expression in ratessionin in rate HSC.JNK and p38 mitogen-activated protein kinases （MAPKs） are involved in IL-1β-induced TIMMP-1 gene expression, and play a distinct role in this process, indicating that p38 and .INK pathways cooperatively mediate TIMP-1 mRNA expression in rat HSC.
基金the National Natural Science Foundation of China! (No. 39730440).
文摘Objective: To investigate the synergistic anti-tumor effects of murine IL-12 gene and HSV-TK gene therapy in mice bearing liver cancer. Methods: Mouse liver cancer MM45T. Li (H-2d) cells were transfected with retroviral vector containing IL-12 gene or HSV-TK gene insert. Gene-modified liver cancer cells, MM45T. Li/IL-12 and MM45T. Li/TK, with stable expression of IL-12 and TK were obtained. Balb/c mice were inoculated subcutaneously with 2′105 MM45T. Li cells. When the tumor reached a size of 0.5-1.0 cm, a mixture of MM45T.Li/TK cells and 60Co-irradiated MM45T. Li/IL-12 cell were injected intratumoraly. Ganciclovir (GCV) was injected ip (40 mg.kg-1.d-1) for 10 days. Intratumoral injection of 60Co-irradiated MM45T. Li/IL-12 cells was repeated twice in one week apart. Mice with distant tumors were treated according to the same protocol. CTL activity of spleen cells was measured by 51Cr-release assay and phenotype of tumor infiltrating lymphocytes by immunohistochemical staining. Results: In mice treated with MM45T. Li/IL-12 or MM45T. Li/TK+GCV individually led to moderate reduction in tumor growth, but neither could eradicate the tumor completely, while in 60% of mice treated with a mixture of MM45T. Li/IL-12 and MM45T. Li/TK cells plus GCV, complete tumor regression was observed, with no tumor recurrence for two months. The growth of distant tumor was also inhibited significantly in mice similarly treated. Most of the mice received combined gene therapy plus GCV had abundant CD4+, CD8+T lymphocyte infiltration. Their CTL activity was significantly higher than in mice received single gene therapy. Conclusion Combination therapy with IL-12 gene and HSV-TK gene plus GCV is effective for mouse liver cancer.
基金Supported by Millitary Medicine and Health Foundation of China, No. 08Z030
文摘AIM: To compare the influence of different transplant sites in bone marrow mesenchymal stem cell (MSC)-based therapy for liver fibrosis. METHODS: MSCs isolated from Sprague Dawley (SD) rats were induced into hepatocyte-like cells. Liver fibrosis in SD rats was induced with carbon tetrachloride. Following hepatocyte induction in vitro, 4',6-diamidino- 2-phenylindole (DAPI)-labeled MSCs were transplanted by intravenous, intrahepatic, and intraperitoneal injection. Histopathological staining, immunohistochemistry, and biochemical analysis were used to compare the morphological and functional liver regeneration among different MSC injection modalities. The expression differences of interleukins, growth factor, extracellular matrix, matrix metalloproteinases, and tissue inhibitor of metalloproteinase were examined by real-time reverse transcription-polymerase chain reaction (RT-PCR) andenzyme linked immunosorbent assay (ELISA). RESULTS: Four days after exposure to hepatocyte differentiation medium, MSCs that did not express hepatocyte markers could express α-fetoprotein, albumin, and cytokeratin 18. The results of histopathological staining, immunohistochemistry, and biochemical analysis indicated that intravenous injection is more effective at rescuing liver failure than other injection modalities. DAPI-labeled cells were found around liver lobules in all three injection site groups, but the intravenous group had the highest number of cells. PCR and ELISA analysis indicated that interleukin-10 (IL-10) was highest in the intravenous group, whereas il1β, il6, tnfα and tgfβ, which can be regulated by IL10 and are promoters of liver fibrosis, were significantly lower than in the other groups. CONCLUSION: MSC administration is able to protect against liver fibrosis. Intravenous injection is the most favorable treatment modality through promotion of IL10 expression.
基金Supported by The German Research FoundationNo.DFG Ta434/2-1 and SFB/TRR57the Interdisciplinary Center for Clinical Research(IZKF) Aachen
文摘Conventional adaptive T cell responses contribute to liver inflammation and fibrogenesis,especially in chronic viral infections and autoimmune hepatitis.However,the role of unconventional gamma-delta(γδ)T cells in liver diseases is less clear.In the past two decades,accumulating evidence revealed thatγδT cell numbers remarkably increase in the liver upon various inflammatory conditions in mice and humans.More recent studies demonstrated that the functional effect ofγδT cells on liver disease progression depends on the subsets involved,which can be identified by the expression of distinct T cell receptor chains and of specific cytokines.Fascinatingly,γδT cells may have protective as well as pathogenic functions in liver diseases.Interferonγ-producingγδT cells,for example,induce apoptosis in hepatocytes but also in hepatic tumor cells;while interleukin-17-expressingγδT cells can downregulate pathogenic effector functions of other immune cells and can promote apoptosis of fibrogenic stellate cells.However,the results obtained in human liver disease as well as murine models are not fully conclusive at present,and the effects ofγδT cells on the outcome of liver disease might vary dependent on etiology and stage of disease.Further definitions of theγδT cell subsets in-volved in acute and chronic liver inflammation,as well as their effector cytokines might uncover whether interference withγδT cells could be a useful target for the treatment of liver disease.
基金National Natural Science Foundation of China,No.39970831.
文摘AIM: To identify the property of dendritic cells (DCs) of peripheral blood monocytes (PBMC) in patients with chronic HBV infection. METHODS: Twenty patients with persistent HBV infection were included in this study, 10 healthy subjects being used as a control group. The peripheral blood mononuclear cells (PBMC) of T cell-depleted populations were incubated and induced into mature dendritic cells in the RPMI-1640 medium in the presence of cytokines GM-CSF, IL-4, FLt-3,TNF-alpha and 100mL.L(-1 )of fetal calf serum for a total of 10-12 days. The expressions of surface markers on DCs were evaluated using flow cytometric analysis. ELISA method was used to determine the cytokine levels of interleukin-12 (IL-12) and IL-10 in the supernatant produced by DCs. For detection of the stimulatory capacity of DCs to T cell proliferation, mytomycin C-treated DC were incubated with allogenic T cells. RESULTS: A typical morphology of mature DCs from healthy subjects and HBV-infected patients was induced in in vitro incubation, but the proliferation ability and cellular number of DCs from HBV-infected patients significantly decreased compared with healthy individuals. In particular, the expression levels of HLA-DR, CD80 (B7-1) and CD86 (B7-2) on DC surface from patients were also lower than that from healthy individuals (0.46 vs 0.92 for HLA-DR, 0.44 vs 0.88 for CD80 and 0.44 vs 0.84 for CD86,P【0.05). The stimulatory capacity and production of IL-12 of DCs from patients in allogenic mixed lymphocyte reaction (AMLR) significantly decreased, but the production level of nitric oxide (NO) by DCs simultaneously increased compared with healthy subjects (86 +/- 15 vs 170 +/- 22 micromol.L(-1), P 【0.05). CONCLUSION: The patients with chronic HBV infection have the defective function and immature phenotype of dendritic cells, which may be associated with the inability of efficient presentation of HBV antigens to host immune system for the clearance of HBV.
基金a generous grant of the Joachim Kuhlinann AIDS-Stiftung
文摘AIM:Cytokine release by macrophages critically determines the type of immune response to an antigen.Therefore,we studied hepatitis C virus(HCV)-specific induction of interleukins-1β,-10,-12(IL-1β,IL-10,IL-12),and tumor necrosis factor-α(TNF-α)in monocytes. METHODS:Intracallular cytokine expression was studied by flow cytometry in 23 patients with chronic hepatitis C,14 anti-HCV seropositives without viremia and 11 controls after stimulation of peripheral blood mononuclear calls with recombinant core,NS3,NS4,NSSa and NSSb proteins. RESULTS:Patients with HCV viremia revealed greater spontaneous expression of IL-1β,TNF-α,and IL-10. Furthermore,greater than twofold higher IL-10 expression was induced by the HCV antigens in chronic hepatitis C than in the other two groups(P<0.05).In contrast,neither IL- 12 nor TNF-α was induced preferentially. CONCLUSION:In chronic hepatitis C antigen-specific cytokine induction in monocytes is apparently shifted towards predominant IL-10 induction-not counterbalanced by antiviral type 1 cytokines.This may contribute to persistent viral replication.
文摘AIM: To assess vitamin D in hepatitis C patients and its relationship to interleukin (IL)-23, IL-17, and macrophage chemoattractant protein-1 (MCP-1). METHODS: The study was conducted on 50 Egyptian hepatitis C virus (HCV) genotype number IV-infected patients and 25 age- and gender-matched healthy subjects. Venous blood samples were obtained. Samples were allowed to clot and sera were separated by centrifugation and stored at -20?°C. A 25 hydroxy vitamin D assay was carried out using solid phase RIA. A 1,25 dihydroxy vitamin D assay was carried out using a commercial kit purchased from Incstar Corporation. IL-17 and -23 and MCP-1 were assayed by an enzyme immunoassay. Quantitative and qualitative polymerase chain reaction for HCV virus were done by TaqMan technology. Only HCV genotype IV-infected subjects were included in the study. The mean ± SD were determined, a t-test for comparison of means of different parameters was used. Correlation analysis was done using Pearson’s correlation. Differences among different groups were determined using the Kruskal-Wallis test. RESULTS: The mean vitamin D level in HCV patients (group?I) was 15 ± 5.2 ng/mL while in control (group II) was 39.7 ± 10.8. For active vitamin D in group?I?as 16.6 ± 4.8 ng/mL while in group II was 41.9 ± 7.9. IL-23 was 154 ± 97.8 in group?I?and 6.7 ± 2.17 in group II. IL-17 was 70.7 ± 72.5 in cases and 1.2 ± 0.4 in control. MCP-1 was 1582 ± 794.4 in group?I?and 216.1 ± 5.38 in group II. Vitamin D deficiency affected 72% of HCV-infected patients and 0% of the control group. Vitamin D insufficiency existed in 28% of HCV-infected patients and 12% of the control group. One hundred percent of the cirrhotic patients and 40% of non cirrhotic HCV-infected patients had vitamin D deficiency. IL-23, IL-17, and MCP-1 were markedly increased in HCV-infected patients in comparison to controls.A significant negative correlation between vitamin D and IL-17 and -23 and MCP-1 was detected. HCV-infected males and females showed no differences with respect to viral load, vitamin D levels, IL-17, IL-23 and MCP-1. The viral load was negatively correlated with vitamin D and active vitamin D (P = 0.0001 and P = 0.001, respectively), while positively correlated with IL-23, IL-17, and MCP-1. We classified the patients according to sonar findings into four groups. Group?Ia with bright hepatomegaly and included 14 patients. Group?Ib with perihepatic fibrosis and included 11 patients. Group?Ic with liver cirrhosis and included 11 patients. Group?Id with hepatocellular carcinoma (HCC) and included 14 patients. Vitamin D and active vitamin D were shown to be lower in cirrhotic patients and much lower in patients with HCC, and this difference was highly significant (P = 0.0001). IL-17 and -23 and MCP-1 were higher in advanced liver disease) and the differences were highly significant (P = 0.0001). CONCLUSION: Whether the deficiency of vitamin D is related to HCV-induced chronic liver disease or predisposing factor for higher viral load is a matter of debate.
文摘AIM: To investigate the association of the functional monocyte chemotactic protein-1 (MCP-1) promoter polymorphism (A-2518G) with spontaneous bacterial peritonitis (SBP).
基金The Science and Technology Bureau of Wuhan,China(No.2015061701011646)the Key Projects of the Hubei Provincial Education Department(No.D20112001)。
文摘OBJECTIVE:To investigate the mechanism by which Daifan San(DFS)prevents and treats primary biliary cirrhosis(PBC)via the forkhead box P3(FoxP3)and interleukin(IL)-23/IL-17A signaling pathways.METHODS:Ninety C57BL/6 mice were randomly divided into the control,model,DFS low-dose,DFS middle-dose,DFS high-dose and ursodeoxycholic acid(UDCA)groups(n=15 per group).A mouse model of PBC was induced using polyinosinic polycytidylic acids(poly I:C).Lymphocyte subset expression in the peripheral blood was analyzed via flow cytometry.The inflammatory cytokines and antimitochondrial autoantibody(AMA)levels were detected via enzyme-linked immunosorbent assays.The expressions and location of typeⅠcollagen,typeⅢcollagen,cytokeratin 19 and FoxP3 in the liver tissue were evaluated via immunohistochemistry.FoxP3,IL-23 and IL-17 expressions in the peripheral blood and liver tissue were evaluated via real-time polymerase chain reaction and western blotting.RESULTS:IL-17,IL-23,IL-8,IL-33,TNF-α,and AMA expressions were significantly increased in the model group and decreased in the DFS and UDCA groups.Conversely,Treg cell and FoxP3 expressions were significantly decreased in the model group and increased in the DFS and UDCA groups.The IL-23/IL-17A signaling pathway was closely correlated with chronic inflammation of the bile duct in PBC and functional deletion of Treg cells,leading to reduced FoxP3 levels and mediating the loss of tolerance in PBC.CONCLUSION:DFS may delay the occurrence and relieve the symptoms of PBC by downregulating IL-23/IL-17A signaling pathway expression and upregulating FoxP3 expression.
基金Supported by The German Research Foundation(DFG Ta434/3-1 and SFB/TRR57)by the Interdisciplinary Center for Clinical Research(IZKF)Aachen
文摘Myeloid derived suppressor cells(MDSC) are a heterogeneous population of immune cells that are potent suppressors of immune responses. MDSC emerge in various compartments in the body, such as blood, bonemarrow or spleen, especially in conditions of cancer, infections or inflammation. MDSC usually express CD11 b, CD33, and low levels of human leukocyte antigen-DR in humans or CD11 b and Gr1(Ly6C/G) in mice, and they can be further divided into granulocytic or monocytic MDSC. The liver is an important organ for MDSC induction and accumulation in hepatic as well as extrahepatic diseases. Different hepatic cells, especially hepatic stellate cells, as well as liver-derived soluble factors, including hepatocyte growth factor and acute phase proteins(SAA, KC), can promote the differentiation of MDSC from myeloid cells. Importantly, hepatic myeloid cells like neutrophils, monocytes and macrophages fulfill essential roles in acute and chronic liver diseases. Recent data from patients with liver diseases and animal models linked MDSC to the pathogenesis of hepatic inflammation, fibrosis and hepatocellular carcinoma(HCC). In settings of acute hepatitis, MDSC can limit immunogenic T cell responses and subsequent tissue injury. In patients with chronic hepatitis C, MDSC increase and may favor viral persistence. Animal models of chronic liver injury, however, have not yet conclusively clarified the involvement of MDSC for hepatic fibrosis. In human HCC and mouse models of liver cancer, MDSC are induced in the tumor environment and suppress anti-tumoral immune responses. Thus, the liver is a primary site of MDSC in vivo, and modulating MDSC functionality might represent a promising novel therapeutic target for liver diseases.
基金funded by regular grants and joint grant(File No.0096/2018/A3,0111/2020/A3 and 0056/2020/AMJ)Dr.Neher’s Biophysics Laboratory for Innovative Drug Discovery(File No.001/2020/ALC)+4 种基金supported by the Macao Science and Technology Development Fundsupported by 2020 Young Qihuang Scholar funded by the National Administration of Traditional Chinese Medicinesupported by National Natural Science Foundation of China(82025036)supported by the Start-up Research Grant of University of Macao(SRG2022-00020-FHS,China)the Faculty of Health Science,University of Macao(Macao,China).
文摘Sepsis-induced liver injury(SILI)is an important cause of septicemia deaths.BaWeiBaiDuSan(BWBDS)was extracted from a formula of Panax ginseng C.A.Meyer,Lilium brownie F.E.Brown ex Miellez var.viridulum Baker,Polygonatum sibiricum Delar.ex Redoute,Lonicera japonica Thunb.,Hippophae rhamnoides Linn.,Amygdalus Communis Vas,Platycodon grandiflorus(Jacq.)A.DC.,and Cortex Phelloderdri.Herein,we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota.BWBDS protected mice against SILI,which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity.BWBDS selectively promoted the growth of Lactobacillus johnsonii(L.johnsonii)in cecal ligation and puncture treated mice.Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects.Notably,L.johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity,increasing interleukin-10+M2 macrophage production and enhancing intestinal integrity.Furthermore,heat inactivation L.johnsonii(HI-L.johnsonii)treatment promoted macrophage anti-inflammatory activity and alleviated SILI.Our findings revealed BWBDS and gut microbiota L.johnsonii as novel prebiotic and probiotic that may be used to treat SILI.The potential underlying mechanism was at least in part,via L.johnsonii-dependent immune regulation and interleukin-10+M2 macrophage production.
基金Supported by Agencia Nacional de Promoción Científica y Tecnológica,No.PICT 2008-763,PICT 2011-732by the National University of San Luis(Project 0401)+1 种基金by the Scientific Career of National Council of Scientific and Technical Investigationsby National Council of Scientific and Technical Investigations
文摘Reactive arthritis （ReA）, also known as sterile postin-fectious arthritis, belongs to the group of related ar-thropathies known as spondyloarthritis （SpA）. ReA can arise 1-4 wk after a gastrointestinal or genitourinary infection, but once arthritis develops, the microorgan-ism is not found in the joint. The classical microbes as-sociated with ReA development include Gram-negative aerobic or microaerophilic bacteria containing LPS in their outer membrane. The immunopathogenic mechanisms involved in ReA development are still unknown. A hypothesis suggested that the bacteria probably persist outside the joint, at sites such as gut mucosa or lymph nodes, and bacterial antigens might then be transported to the joints. On the other hand, an altered immune response and the unbalanced production of cy-tokines have been reported in subjects with ReA. Currently, there is increased evidence to suggest that both mechanisms would operate in the immunopathogenesis of ReA. In this review we highlight recent advances on the role of cytokines in the ReA. Particularly, we discuss the roles of some pro- and anti-infammatory cytokines involved in the immunopathogenesis of ReA.
文摘Available reports suggest that, Leishmania donovani antigen KMP-11 may be significant in the modulation of immune responses in visceral leishmaniasis (VL). This study evaluated vaccine prospect of presentation of KMP-11 antigen through murine dendritic cells against VL in infected BALB/c mice. We report here that immunization with KMP-11 delivered through bone marrow derived dendritic cells can lead to killing of L. donovani in infected BALB/c mice. Furthermore, the strategy to use KMP-11 as vaccine delivered through DCs can stimulate the production of IFN-g, IL-12, IL-2R and TNF-α with concomitant down-regulation of IL-10 and IL-4. Furthermore, anti-leishmanial defence function (ROS) of splenocytes was observed increased in the presence of DC-delivered KMP-11 vaccination accompanied with an increased p38-MAPK signalling in vaccinated splenocytes. We summarized from our data that KMP-11 delivered through DCs has potential for eliciting protective immunity through pro-inflammatory cytokines (IFN-γ, IL-12, IL-2, TNF-α) following an up-regulation in signalling event of p38-MAPK. Therefore the study suggests a new control strategy against VL in future.
