Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(...Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.展开更多
Previous studies reported the association between interleukin-6(IL-6)-174G/C gene polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus(T2DN).However,the results remain controversial.In the pre...Previous studies reported the association between interleukin-6(IL-6)-174G/C gene polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus(T2DN).However,the results remain controversial.In the present study,we conducted a meta-analysis to further examine this relationship between IL-6-174G/C gene polymorphism and T2DN.Three databases(PubMed,SinoMed and ISI Web of Science)were used to search clinical case-control studies about IL-6-174G/C polymorphism and T2DN published until Apr.14,2018.Fixed-or random-effects n lodels were used to calculate the effect sizes of odds ratio(OR)and 95%confide nee intervals(95%CI).Moreover,subgroup analysis was performed in tenns of the excretion rate of albuminuria.All the statistical analyses were con ducted using Stata 12.0.A total of 11 case-control studies were included in this study,involving 1203 cases of T2DN and 1571 cases of T2DM without DN.Metaanalysis showed that there was an association between IL-6-174G/C polymorphism and increased risk of T2DN under the allelic and recessive genetic models(G vs.C:OR=1.10,95%CI 1.03-1」&P=0.006;GG vs.CC+GC:OR=1.11,95%CI 1.02-1.21,P=0.016).In the subgroup analysis by albuminuria,a significant association of IL-6-174G/C polymorphism with risk of T2DN was noted in the microalbuminuria group under the recessive model(OR=1.54,95%CI 1.02-2.32,P=0.038).In conclusion,this meta-analysis suggests that IL-6-174G/C gene polymorphism is associated with the risk of T2DN.展开更多
The current study sought to investigate the potential protective action of curcumin against interleukin-6-induced injury in rat hippocampal neurons. The results revealed that interleukin-6 induced typical cellular inj...The current study sought to investigate the potential protective action of curcumin against interleukin-6-induced injury in rat hippocampal neurons. The results revealed that interleukin-6 induced typical cellular injury, such as the swelling of cell bodies and increased Ca^2+ concentration. After administration of curcumin, interleukin-6-induced neurons recovered to a normal state, and the fluorescence intensity of Ca^2+ gradually returned to normal. These findings suggest that curcumin exerts a protective effect on hippocampal neurons of rats. In addition, our results suggest that the protective effect of curcumin involves prevention of the rapid Ca^2+ influx induced by interleukin-6, which maintains Ca^2+ homeostasis.展开更多
[ Objective] To understand the functions of interteukin-2 (IL-2) and interleukin-6 (IL-6) in immune response. [ Method] Peripheral lymphocytas were isolated from a hybrid pig ( Duroc x Landrace x Shandong local ...[ Objective] To understand the functions of interteukin-2 (IL-2) and interleukin-6 (IL-6) in immune response. [ Method] Peripheral lymphocytas were isolated from a hybrid pig ( Duroc x Landrace x Shandong local pig) and stimulated with canavalin A in vitro. With total RNA as templates, the IL-2 and IL-6 cDNA were amplified by the RT-PCR and sequenced, respectively. [Result] The sequence of IL-2 gene had 100.0% nucleotide homology to the published IL-2 sequences. The sequence of IL-6 gene had 99.8% -100.0% nucleotide homology to the published IL-6 sequences, and the amino acid homology was 99.1% -100.0%. [ Conclusion] NO great variation of the IL-2 gene and IL-6 gene is observed in the hybdd pig, and these results provide a basis for research about functions of IL-2 and IL-6 protein.展开更多
Since December 2019,a novel coronavirus that represents a serious threat to human lives has emerged.There is still no definite treatment for severe cases of the disease caused by this virus,named coronavirus disease 2...Since December 2019,a novel coronavirus that represents a serious threat to human lives has emerged.There is still no definite treatment for severe cases of the disease caused by this virus,named coronavirus disease 2019(COVID-19).One of the most considered treatment strategies targets the exaggerated immune regulator,and interleukin(IL)-6 is a crucial pro-inflammatory mediator.Severe acute respiratory syndrome coronavirus 2(SARSCoV-2)cases show an elevated level of IL-6 related to disease severity.IL-6 activity can be inhibited by the following:IL-6 itself,IL-6 signaling pathways such as Janus kinase and signal transducer and activator of transcription(JAK-STAT),gp130,IL-6R,and downstream activated ILs,such as IL-17 and IL-6 cytokine.Currently,according to these studies and their results,IL-6 blockade with anti-IL-6 or its receptor antibodies such as tocilizumab in COVID-19 is beneficial in severe cases and may reduce the mortality rate.JAK-STAT inhibitors block the cytokine storm by inhibiting several crucial pro-inflammatory mediators such as TNF-αand IL-6 and have shown various results in clinical trials.IL-6 induces IL-17 secretion,and IL-17 is involved in the pathogenesis of inflammatory processes.Clinical trials of anti-IL-17 drugs are currently recruiting,and anti-gp130 antibody is preclinical.However,this agent has shown positive effects in inflammatory bowel disease clinical trials and could be tested for SARS-CoV-2.This study aimed to review the role of IL-6 in the cytokine storm and studies regarding IL-6 and blockade of its inflammatory pathways in COVID-19 to determine if any of these agents are beneficial for COVID-19 patients.展开更多
The ability of human recombinant interleukin-6 (IL-6) to regulate the induction and cytotoxic function of lymphokine activated killer (LAK) cells from human fetal spleen was studied. The results showed that IL-6 alone...The ability of human recombinant interleukin-6 (IL-6) to regulate the induction and cytotoxic function of lymphokine activated killer (LAK) cells from human fetal spleen was studied. The results showed that IL-6 alone was unably to Induce fetal splenic mononuclear cells (FSMC) to develop functional LAK cells, nor was it able to affect the number of IL-2-induced LAK cells and to alter the lytic activity of LAK cells against tumor cells in effector phase. However, when IL-6 was used in combination with IL-2 during the induction phase , the resulting LAK cells displayed considerably greater lytic, activity than that with IL-2 alone (P<0. 01), and this effect was IL-6 dose-dependent. The possible machanism of the synergistic effect of IL-2 and IL-6 in LAK cell Induction from human fetal spleen is discussed.展开更多
Porcine interleukin-2 and porcine interleukin-6 cDNA sequences were cloned into the expressing vectors pET-28a and pGEX-KG respectively. They were expressed in E. coli BL21(DE3)with high-level production. The gene del...Porcine interleukin-2 and porcine interleukin-6 cDNA sequences were cloned into the expressing vectors pET-28a and pGEX-KG respectively. They were expressed in E. coli BL21(DE3)with high-level production. The gene deleted vaccine of pseudorabies virus Ea strain(TK-/gG-/LacZ+)was mixed with the two different purified recombinant proteins each, or both, with the doses of 2, 5 or 10 μg ml-1. Ten groups of pseudorabies negative antibody swines were immuned twice with tested vaccines with different doses, or control vaccine, respectively. The antibody liters of the test groups were detected by neutralization test, and the daily weight gains of swines were calculated and analyzed statistically. In the study, all the neutralizing antibody ti-ters in test groups were higher than the control group, and the recombinant proteins appeared a dose dependent adjuvant effect. The tested vaccines with 2 μg ml-1 pIL-2 and with 10 μg ml-1 pIL-2/pIL-6 got significant and extremely significant differences, compared with the vaccines without pILs. The difference of the daily weight gain indicated the potential positive influence of pIL-2 and pIL-6 on immune protection.展开更多
Objectives: To observe the plasmatic concentration of IL-6, IL-10 and IL-2 in the patient of chronic allergic rhinitis before and after acupuncture therapy. Methods: Cytokine levels were determined before and after tr...Objectives: To observe the plasmatic concentration of IL-6, IL-10 and IL-2 in the patient of chronic allergic rhinitis before and after acupuncture therapy. Methods: Cytokine levels were determined before and after treatment in 30 healthy volunteers (Group A) and 90 patients of chronic allergic rhinitis (Group B) with an increased plasma IL-10 level. Group B was then divided into 3 subgroups: 30 patients treated with real acupuncture (Group B1); 30 patients treated with sham acupuncture (Group B2); 30 non-treated patients (Group B3). Results: The allergic subjects of group B1, compared with controls, showed a significant reduction of IL-10 after a specific treatment with acupuncture (P<0.05). On the other hand, in those patients treated with sham acupuncture (B2) as well as in non-treated patients (B3), the IL-10 values remained high and unchanged. There was a statistically significant change in IL-2 values at 24 hours (P<0.05) after real acupuncture (Groups A, B1), however the values remained within normal ranges. The IL-6 do not change after therapy. Conclusion: The acupuncture treatment can reduce plasmatic level of IL-10 in chronic allergic rhinitis.展开更多
Severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)infection can lead to a cytokine storm,unleashed in part by pyroptosis of virus-infected macrophages and monocytes.Interleukin-6(IL-6)has emerged as a key par...Severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)infection can lead to a cytokine storm,unleashed in part by pyroptosis of virus-infected macrophages and monocytes.Interleukin-6(IL-6)has emerged as a key participant in this ominous complication of coronavirus disease 2019(COVID-19).IL-6 antagonists have improved outcomes in patients with COVID-19 in some,but not all,studies.IL-6 signaling involves at least 3 distinct pathways,including classic-signaling,trans-signaling,and trans-presentation depending on the localization of IL-6 receptor and its binding partner glycoprotein gp130.IL-6 has become a therapeutic target in COVID-19,cardiovascular diseases,and other inflammatory conditions.However,the efficacy of inhibition of IL-6 signaling in metabolic diseases,such as obesity and diabetes,may depend in part on cell type-dependent actions of IL-6 in controlling lipid metabolism,glucose uptake,and insulin sensitivity owing to complexities that remain to be elucidated.The present review sought to summarize and discuss the current understanding of how and whether targeting IL-6 signaling ameliorates outcomes following SARS-CoV-2 infection and associated clinical complications,focusing predominantly on metabolic and cardiovascular diseases.展开更多
Ramulus Cinnamomi (RC), a traditional Chinese herb, has been used to attenuate inflammatory responses. The purpose of this study was to investigate the effect of RC extract on lipopolysaccharide (LPS)-induced neur...Ramulus Cinnamomi (RC), a traditional Chinese herb, has been used to attenuate inflammatory responses. The purpose of this study was to investigate the effect of RC extract on lipopolysaccharide (LPS)-induced neuroinflammation in BV2 microglial cells and the underlying mechanisms involved. BV2 cells were incubated with normal medium (control group), LPS, LPS plus 30 pg/mL RC extract, or LPS plus 100 pg/mL RC extract. The BV2 cell morphology was observed under an optical microscope and cell viability was detected by MTT assay. Nitric oxide level in BV2 cells was detected using Griess regents, and the levels of interleukin-6, interleukin-1 β, and tumor necrosis factor u in BV2 cells were determined by ELISA. The expression levels of cyclooxygenase-2, Toll-like receptor 4 and myeloid differentiation factor 88 proteins were detected by western blot assay. Compared with the LPS group, both 30 and 100 μg/mL RC extract had no significant effect on the viability of BV2 cells. The levels of nitric oxide, interleukin-6, interleukin-1β and tumor necrosis factor ct in BV2 cells were all significantly increased after LPS induction, and the levels were significantly reversed after treatment with 30 and 100 μg/mL RC extract. Furthermore, RC extract significantly inhibited the protein expression levels of cyclooxygenase-2, Toll-like receptor 4 and myeloid differentiation factor 88 in LPS-induced BV2 cells. Our findings suggest that RC extract alleviates neuroinflammation by downregulating the TLR4/MyD88 signaling pathway.展开更多
Objective: To evaluate effects of docosahexaenoic acid-enriched phosphatidylcholine(DHAPC) on cytokine production induced by lipopolysaccharide(LPS). Methods: The culture supernatants of splenocytes exposed to DHA-PC ...Objective: To evaluate effects of docosahexaenoic acid-enriched phosphatidylcholine(DHAPC) on cytokine production induced by lipopolysaccharide(LPS). Methods: The culture supernatants of splenocytes exposed to DHA-PC along with LPS were harvested to determine the production of Th 1(IFN-kines. Cytokines were m毭 and IL-2) and Th2 [IL-4, IL-5, IL-6 and IL-12/IL-23(p40)] cytoeasured using ELISA. Results: Co-administration of DHAPC with LPS resulted in significantly lower IL-2 expression compared to that observed with administration of only LPS(P<0.01). Treatment with DHA-PC and LPS significantly increased IL-5 expression(P<0.01). Moreover, co-administration of DHA-PC with LPS significantly decreased IL-6 and IL-12/IL-23(p40) expressions compared to that observed with administration of only LPS(P<0.01). Conclusions: Our results suggest that DHA-PC inhibits pro-inflammatory cytokines [IL-2, IL-6 and IL-12/IL-23(p40)] expression on induction of inflammation.展开更多
Objective:To investigate the expression of cyclooxygenase-2 and its pathological effect in the experimental nonalcoholic fatty liver of rats, and to explore its possible mechanism. Methods:The rat NAFLD model was es...Objective:To investigate the expression of cyclooxygenase-2 and its pathological effect in the experimental nonalcoholic fatty liver of rats, and to explore its possible mechanism. Methods:The rat NAFLD model was established by giving a fat-enriched diet. The blood samples were obtained form abdominal aorta and the levels of serum ALT, AST and IL-1, changes in the hepatic tissue 6-k-PGF1 α TXB2 were measured. The expression level of COX-2 in rats livers were assayed by immunohistochemistry, RT-PCR and Westernblot. Results: Light microscope analysis revealed that hepatocytes were injured in the model group and slightly in the treatment group. The levels of serum TXB2 and IL-1 in the fatty liver rats were increased. Compared with the model group, the IL-1 and TXB2 increased significantly(P〈 0.05), on the contrary, compared with the normal group, the hepatic tissue 6-Keto-prostagland decreased significantly in the model group(P 〈 0.05), the treatment group also increased but P 〉 0.05. There was no positive expression of COX-2 in hepatic tissue of normal rats. In the model group, there was positive expression of COX-2 antigen and the number of COX positive cells progressively increased at 4, 8, 12 wks. The intensity of expression of COX-2 had significantly increased(P 〈 0.05 ) and the intensity of COX-2 expression in the treated group decreased remarkably compared with the model group(P 〈 0.05). The expression of COX-2 mRNA and the level of COX-2 protein were significantly stronger in the liver of model rats compared with normal rats, and significantly weaker in treated rats, than in 8W and 12W model rats(P 〈 0.05). Conclusion:The increase of COX-2 expression in NAFLD is closely associated with the severity of liver inflammation and damage. COX-2 may play an important role in the progression of rat NAFLD, and the expression of COX-2 mRNA is downregulated by cyclooxygenase-2 inhibitor, which can depress the oxidative stress and control inflammatory response efficiently.展开更多
The study examined the inhibitory effect of Atractylodes macrocephala (AM) on the uterine contraction during premature delivery and explored its electrophysiological mechanism by studying the effects of AM on the C...The study examined the inhibitory effect of Atractylodes macrocephala (AM) on the uterine contraction during premature delivery and explored its electrophysiological mechanism by studying the effects of AM on the Ca^2+-activated K^+ currents of pregnant human myometrial smooth muscle cells with or without the treatment with intedeukin-6. Single cells were acutely isolated from pregnant human myometrial smooth muscles. Whole-cell Ca^2+-activated K^+ currents were recorded by using an Axopatchl-D amplifier. The cells were divided into three groups: group A in which AM was added into perfusate, group B, in which interleukin-6 was added into perfusate) and group C in which AM was added into perfusate after addition of interleukin-6. IL-6 10 ng/mL inhibited BKca by 36.9%±13.7% as compared with control (P〈0.01). AM at 2 mg/mL raised BKca by 36.7%±22.6% or 45.2%±13.7% with or without the treatment of IL-6, respectively (P〈0.01). It is concluded that AM was able to enhance the BKca of pregnant human myometrial smooth muscle cells treated or untreated with interleukin-6 and its effect on the BKca IL-treated cells was stronger that its effect on BKca of untreated cells. Our results suggested that AM can help to maintain the membrane potentials and the resting status of pregnant human myometrial smooth muscle cells.展开更多
OBJECTIVE The present study aimed to investigate the relationship between Wnt/β-catenin and Nrf2 signaling pathways,and understanding the mechanisms underlying the process of inflammatory in chronic obstructive pulmo...OBJECTIVE The present study aimed to investigate the relationship between Wnt/β-catenin and Nrf2 signaling pathways,and understanding the mechanisms underlying the process of inflammatory in chronic obstructive pulmonary disease(COPD),which was a serious disease of respiratory system.METHODS We duplicate the emphysema model with porcine pancreatic elastase(PPE)in Nrf2-/-and WT mouse for 21d,and intraperitoneal injection of Li Cl,the activator of Wnt/β-catenin signaling pathway from 14 d to the end.Hematoxylin and eosin(H&E)staining was performed to assess the histopathologic level,and immunohistochemistry(IHC)for Mac-3(the marker of macrophagocyte)and Ly6G(the marker of neutrophil)was used to observe the inflammatory infiltrate,while the levels of Wnt/β-catenin and Nrf2 signaling pathways related proteins heme oxygenase-1(HO-1),NAD(P)H:quinone oxidoreductase 1(NQO1),and the expression of inflammatory cytokine interleukin-6(IL-6)were detected by Western blotting of lung tissues.In vitro,cigarette smoke extract(CSE)-treated normal human bronchial epithelial(NHBE)cells,cell viability was examined by MTT assay,and then we treated recombinant human Wnt3a,si Nrf2 and si Wnt3a to measure the expression of Wnt3a,β-catenin,Nrf2,HO-1,NQO-1,and IL-6.Cellular immunofluorescence staining was employed to identify the nuclear translocation of Nrf2.RESULTS We found that the Li Cl-treated group has markedly decreased the damage of alveolar structure and inflammatory signs than the model group of WT mice rather than Nrf2-/-group.It also seen that Li Cl not only increasedβ-catenin,but it also led to a comparable increase in Nrf2,HO-1,NQO1,and decrease of IL-6 compared with WT model groups but except to Nrf2-/-group in vivo.And it showed that Wnt3atreatment has significantly increased the nuclear translocation of Nrf2 and the expression of HO-1 and NQO1,reduced the IL-6 release,while there has no significance when Nrf2 was blocked in CSE-induced NHBE cells.CONCLUSION Our results demonstrated that Wnt3a/β-catenin significantly balanced oxidative stress and attenuated inflammation reaction by promoting Nrf2 nuclear translocation and activity.展开更多
基金The Sixth Batch of Special Support Plans in Anhui Province(No.dlPtzjh20200050)Key Natural Science Research Project of Higher Education Institutions in Anhui Province(No.KJ2020A0426)。
文摘Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.
文摘Previous studies reported the association between interleukin-6(IL-6)-174G/C gene polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus(T2DN).However,the results remain controversial.In the present study,we conducted a meta-analysis to further examine this relationship between IL-6-174G/C gene polymorphism and T2DN.Three databases(PubMed,SinoMed and ISI Web of Science)were used to search clinical case-control studies about IL-6-174G/C polymorphism and T2DN published until Apr.14,2018.Fixed-or random-effects n lodels were used to calculate the effect sizes of odds ratio(OR)and 95%confide nee intervals(95%CI).Moreover,subgroup analysis was performed in tenns of the excretion rate of albuminuria.All the statistical analyses were con ducted using Stata 12.0.A total of 11 case-control studies were included in this study,involving 1203 cases of T2DN and 1571 cases of T2DM without DN.Metaanalysis showed that there was an association between IL-6-174G/C polymorphism and increased risk of T2DN under the allelic and recessive genetic models(G vs.C:OR=1.10,95%CI 1.03-1」&P=0.006;GG vs.CC+GC:OR=1.11,95%CI 1.02-1.21,P=0.016).In the subgroup analysis by albuminuria,a significant association of IL-6-174G/C polymorphism with risk of T2DN was noted in the microalbuminuria group under the recessive model(OR=1.54,95%CI 1.02-2.32,P=0.038).In conclusion,this meta-analysis suggests that IL-6-174G/C gene polymorphism is associated with the risk of T2DN.
基金the Natural Science Foundation of Guangdong Province,No. 06105246, 9151040701000Science and Technology Foundation of Guangzhou,No. 2010Y1-C291+1 种基金Science and Technology Foundation of Guangdong Province,No. 2010B030700016, 2008A030201003Leading Academic Discipline Program,211 Project for Jinan University (The 3 rd Phase)
文摘The current study sought to investigate the potential protective action of curcumin against interleukin-6-induced injury in rat hippocampal neurons. The results revealed that interleukin-6 induced typical cellular injury, such as the swelling of cell bodies and increased Ca^2+ concentration. After administration of curcumin, interleukin-6-induced neurons recovered to a normal state, and the fluorescence intensity of Ca^2+ gradually returned to normal. These findings suggest that curcumin exerts a protective effect on hippocampal neurons of rats. In addition, our results suggest that the protective effect of curcumin involves prevention of the rapid Ca^2+ influx induced by interleukin-6, which maintains Ca^2+ homeostasis.
文摘[ Objective] To understand the functions of interteukin-2 (IL-2) and interleukin-6 (IL-6) in immune response. [ Method] Peripheral lymphocytas were isolated from a hybrid pig ( Duroc x Landrace x Shandong local pig) and stimulated with canavalin A in vitro. With total RNA as templates, the IL-2 and IL-6 cDNA were amplified by the RT-PCR and sequenced, respectively. [Result] The sequence of IL-2 gene had 100.0% nucleotide homology to the published IL-2 sequences. The sequence of IL-6 gene had 99.8% -100.0% nucleotide homology to the published IL-6 sequences, and the amino acid homology was 99.1% -100.0%. [ Conclusion] NO great variation of the IL-2 gene and IL-6 gene is observed in the hybdd pig, and these results provide a basis for research about functions of IL-2 and IL-6 protein.
文摘Since December 2019,a novel coronavirus that represents a serious threat to human lives has emerged.There is still no definite treatment for severe cases of the disease caused by this virus,named coronavirus disease 2019(COVID-19).One of the most considered treatment strategies targets the exaggerated immune regulator,and interleukin(IL)-6 is a crucial pro-inflammatory mediator.Severe acute respiratory syndrome coronavirus 2(SARSCoV-2)cases show an elevated level of IL-6 related to disease severity.IL-6 activity can be inhibited by the following:IL-6 itself,IL-6 signaling pathways such as Janus kinase and signal transducer and activator of transcription(JAK-STAT),gp130,IL-6R,and downstream activated ILs,such as IL-17 and IL-6 cytokine.Currently,according to these studies and their results,IL-6 blockade with anti-IL-6 or its receptor antibodies such as tocilizumab in COVID-19 is beneficial in severe cases and may reduce the mortality rate.JAK-STAT inhibitors block the cytokine storm by inhibiting several crucial pro-inflammatory mediators such as TNF-αand IL-6 and have shown various results in clinical trials.IL-6 induces IL-17 secretion,and IL-17 is involved in the pathogenesis of inflammatory processes.Clinical trials of anti-IL-17 drugs are currently recruiting,and anti-gp130 antibody is preclinical.However,this agent has shown positive effects in inflammatory bowel disease clinical trials and could be tested for SARS-CoV-2.This study aimed to review the role of IL-6 in the cytokine storm and studies regarding IL-6 and blockade of its inflammatory pathways in COVID-19 to determine if any of these agents are beneficial for COVID-19 patients.
文摘The ability of human recombinant interleukin-6 (IL-6) to regulate the induction and cytotoxic function of lymphokine activated killer (LAK) cells from human fetal spleen was studied. The results showed that IL-6 alone was unably to Induce fetal splenic mononuclear cells (FSMC) to develop functional LAK cells, nor was it able to affect the number of IL-2-induced LAK cells and to alter the lytic activity of LAK cells against tumor cells in effector phase. However, when IL-6 was used in combination with IL-2 during the induction phase , the resulting LAK cells displayed considerably greater lytic, activity than that with IL-2 alone (P<0. 01), and this effect was IL-6 dose-dependent. The possible machanism of the synergistic effect of IL-2 and IL-6 in LAK cell Induction from human fetal spleen is discussed.
基金supported by a grant from the National High Tech R&D Program(863 Program)of China(2001AA213051).
文摘Porcine interleukin-2 and porcine interleukin-6 cDNA sequences were cloned into the expressing vectors pET-28a and pGEX-KG respectively. They were expressed in E. coli BL21(DE3)with high-level production. The gene deleted vaccine of pseudorabies virus Ea strain(TK-/gG-/LacZ+)was mixed with the two different purified recombinant proteins each, or both, with the doses of 2, 5 or 10 μg ml-1. Ten groups of pseudorabies negative antibody swines were immuned twice with tested vaccines with different doses, or control vaccine, respectively. The antibody liters of the test groups were detected by neutralization test, and the daily weight gains of swines were calculated and analyzed statistically. In the study, all the neutralizing antibody ti-ters in test groups were higher than the control group, and the recombinant proteins appeared a dose dependent adjuvant effect. The tested vaccines with 2 μg ml-1 pIL-2 and with 10 μg ml-1 pIL-2/pIL-6 got significant and extremely significant differences, compared with the vaccines without pILs. The difference of the daily weight gain indicated the potential positive influence of pIL-2 and pIL-6 on immune protection.
文摘Objectives: To observe the plasmatic concentration of IL-6, IL-10 and IL-2 in the patient of chronic allergic rhinitis before and after acupuncture therapy. Methods: Cytokine levels were determined before and after treatment in 30 healthy volunteers (Group A) and 90 patients of chronic allergic rhinitis (Group B) with an increased plasma IL-10 level. Group B was then divided into 3 subgroups: 30 patients treated with real acupuncture (Group B1); 30 patients treated with sham acupuncture (Group B2); 30 non-treated patients (Group B3). Results: The allergic subjects of group B1, compared with controls, showed a significant reduction of IL-10 after a specific treatment with acupuncture (P<0.05). On the other hand, in those patients treated with sham acupuncture (B2) as well as in non-treated patients (B3), the IL-10 values remained high and unchanged. There was a statistically significant change in IL-2 values at 24 hours (P<0.05) after real acupuncture (Groups A, B1), however the values remained within normal ranges. The IL-6 do not change after therapy. Conclusion: The acupuncture treatment can reduce plasmatic level of IL-10 in chronic allergic rhinitis.
基金supported by the National Heart,Lung,and Blood Institute (HL151627 and HL157073 to Guo-Ping Shi,HL134892 and HL163099 to Peter Libby)the National Institute of Neurological Disorders and Stroke (AG063839 to Guo-Ping Shi).
文摘Severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)infection can lead to a cytokine storm,unleashed in part by pyroptosis of virus-infected macrophages and monocytes.Interleukin-6(IL-6)has emerged as a key participant in this ominous complication of coronavirus disease 2019(COVID-19).IL-6 antagonists have improved outcomes in patients with COVID-19 in some,but not all,studies.IL-6 signaling involves at least 3 distinct pathways,including classic-signaling,trans-signaling,and trans-presentation depending on the localization of IL-6 receptor and its binding partner glycoprotein gp130.IL-6 has become a therapeutic target in COVID-19,cardiovascular diseases,and other inflammatory conditions.However,the efficacy of inhibition of IL-6 signaling in metabolic diseases,such as obesity and diabetes,may depend in part on cell type-dependent actions of IL-6 in controlling lipid metabolism,glucose uptake,and insulin sensitivity owing to complexities that remain to be elucidated.The present review sought to summarize and discuss the current understanding of how and whether targeting IL-6 signaling ameliorates outcomes following SARS-CoV-2 infection and associated clinical complications,focusing predominantly on metabolic and cardiovascular diseases.
基金supported by a grant from the National Natural Science Foundation of China,No.81473383a grant from the Medical and Health Innovation Project of Chinese Academy of Medical Sciences,No.2016-I2M-3-007a grant from Key Project of New-Drugs Creation of Science and Technology of China,No.2012ZX09103101-078 and 2017ZX09101003-003-019
文摘Ramulus Cinnamomi (RC), a traditional Chinese herb, has been used to attenuate inflammatory responses. The purpose of this study was to investigate the effect of RC extract on lipopolysaccharide (LPS)-induced neuroinflammation in BV2 microglial cells and the underlying mechanisms involved. BV2 cells were incubated with normal medium (control group), LPS, LPS plus 30 pg/mL RC extract, or LPS plus 100 pg/mL RC extract. The BV2 cell morphology was observed under an optical microscope and cell viability was detected by MTT assay. Nitric oxide level in BV2 cells was detected using Griess regents, and the levels of interleukin-6, interleukin-1 β, and tumor necrosis factor u in BV2 cells were determined by ELISA. The expression levels of cyclooxygenase-2, Toll-like receptor 4 and myeloid differentiation factor 88 proteins were detected by western blot assay. Compared with the LPS group, both 30 and 100 μg/mL RC extract had no significant effect on the viability of BV2 cells. The levels of nitric oxide, interleukin-6, interleukin-1β and tumor necrosis factor ct in BV2 cells were all significantly increased after LPS induction, and the levels were significantly reversed after treatment with 30 and 100 μg/mL RC extract. Furthermore, RC extract significantly inhibited the protein expression levels of cyclooxygenase-2, Toll-like receptor 4 and myeloid differentiation factor 88 in LPS-induced BV2 cells. Our findings suggest that RC extract alleviates neuroinflammation by downregulating the TLR4/MyD88 signaling pathway.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT and Future Planning(NRF-2017R1A2B4005915)
文摘Objective: To evaluate effects of docosahexaenoic acid-enriched phosphatidylcholine(DHAPC) on cytokine production induced by lipopolysaccharide(LPS). Methods: The culture supernatants of splenocytes exposed to DHA-PC along with LPS were harvested to determine the production of Th 1(IFN-kines. Cytokines were m毭 and IL-2) and Th2 [IL-4, IL-5, IL-6 and IL-12/IL-23(p40)] cytoeasured using ELISA. Results: Co-administration of DHAPC with LPS resulted in significantly lower IL-2 expression compared to that observed with administration of only LPS(P<0.01). Treatment with DHA-PC and LPS significantly increased IL-5 expression(P<0.01). Moreover, co-administration of DHA-PC with LPS significantly decreased IL-6 and IL-12/IL-23(p40) expressions compared to that observed with administration of only LPS(P<0.01). Conclusions: Our results suggest that DHA-PC inhibits pro-inflammatory cytokines [IL-2, IL-6 and IL-12/IL-23(p40)] expression on induction of inflammation.
文摘Objective:To investigate the expression of cyclooxygenase-2 and its pathological effect in the experimental nonalcoholic fatty liver of rats, and to explore its possible mechanism. Methods:The rat NAFLD model was established by giving a fat-enriched diet. The blood samples were obtained form abdominal aorta and the levels of serum ALT, AST and IL-1, changes in the hepatic tissue 6-k-PGF1 α TXB2 were measured. The expression level of COX-2 in rats livers were assayed by immunohistochemistry, RT-PCR and Westernblot. Results: Light microscope analysis revealed that hepatocytes were injured in the model group and slightly in the treatment group. The levels of serum TXB2 and IL-1 in the fatty liver rats were increased. Compared with the model group, the IL-1 and TXB2 increased significantly(P〈 0.05), on the contrary, compared with the normal group, the hepatic tissue 6-Keto-prostagland decreased significantly in the model group(P 〈 0.05), the treatment group also increased but P 〉 0.05. There was no positive expression of COX-2 in hepatic tissue of normal rats. In the model group, there was positive expression of COX-2 antigen and the number of COX positive cells progressively increased at 4, 8, 12 wks. The intensity of expression of COX-2 had significantly increased(P 〈 0.05 ) and the intensity of COX-2 expression in the treated group decreased remarkably compared with the model group(P 〈 0.05). The expression of COX-2 mRNA and the level of COX-2 protein were significantly stronger in the liver of model rats compared with normal rats, and significantly weaker in treated rats, than in 8W and 12W model rats(P 〈 0.05). Conclusion:The increase of COX-2 expression in NAFLD is closely associated with the severity of liver inflammation and damage. COX-2 may play an important role in the progression of rat NAFLD, and the expression of COX-2 mRNA is downregulated by cyclooxygenase-2 inhibitor, which can depress the oxidative stress and control inflammatory response efficiently.
文摘The study examined the inhibitory effect of Atractylodes macrocephala (AM) on the uterine contraction during premature delivery and explored its electrophysiological mechanism by studying the effects of AM on the Ca^2+-activated K^+ currents of pregnant human myometrial smooth muscle cells with or without the treatment with intedeukin-6. Single cells were acutely isolated from pregnant human myometrial smooth muscles. Whole-cell Ca^2+-activated K^+ currents were recorded by using an Axopatchl-D amplifier. The cells were divided into three groups: group A in which AM was added into perfusate, group B, in which interleukin-6 was added into perfusate) and group C in which AM was added into perfusate after addition of interleukin-6. IL-6 10 ng/mL inhibited BKca by 36.9%±13.7% as compared with control (P〈0.01). AM at 2 mg/mL raised BKca by 36.7%±22.6% or 45.2%±13.7% with or without the treatment of IL-6, respectively (P〈0.01). It is concluded that AM was able to enhance the BKca of pregnant human myometrial smooth muscle cells treated or untreated with interleukin-6 and its effect on the BKca IL-treated cells was stronger that its effect on BKca of untreated cells. Our results suggested that AM can help to maintain the membrane potentials and the resting status of pregnant human myometrial smooth muscle cells.
基金The project supported by National Natural Science Foundation of China(81274172,81473267,30801535,81470003)
文摘OBJECTIVE The present study aimed to investigate the relationship between Wnt/β-catenin and Nrf2 signaling pathways,and understanding the mechanisms underlying the process of inflammatory in chronic obstructive pulmonary disease(COPD),which was a serious disease of respiratory system.METHODS We duplicate the emphysema model with porcine pancreatic elastase(PPE)in Nrf2-/-and WT mouse for 21d,and intraperitoneal injection of Li Cl,the activator of Wnt/β-catenin signaling pathway from 14 d to the end.Hematoxylin and eosin(H&E)staining was performed to assess the histopathologic level,and immunohistochemistry(IHC)for Mac-3(the marker of macrophagocyte)and Ly6G(the marker of neutrophil)was used to observe the inflammatory infiltrate,while the levels of Wnt/β-catenin and Nrf2 signaling pathways related proteins heme oxygenase-1(HO-1),NAD(P)H:quinone oxidoreductase 1(NQO1),and the expression of inflammatory cytokine interleukin-6(IL-6)were detected by Western blotting of lung tissues.In vitro,cigarette smoke extract(CSE)-treated normal human bronchial epithelial(NHBE)cells,cell viability was examined by MTT assay,and then we treated recombinant human Wnt3a,si Nrf2 and si Wnt3a to measure the expression of Wnt3a,β-catenin,Nrf2,HO-1,NQO-1,and IL-6.Cellular immunofluorescence staining was employed to identify the nuclear translocation of Nrf2.RESULTS We found that the Li Cl-treated group has markedly decreased the damage of alveolar structure and inflammatory signs than the model group of WT mice rather than Nrf2-/-group.It also seen that Li Cl not only increasedβ-catenin,but it also led to a comparable increase in Nrf2,HO-1,NQO1,and decrease of IL-6 compared with WT model groups but except to Nrf2-/-group in vivo.And it showed that Wnt3atreatment has significantly increased the nuclear translocation of Nrf2 and the expression of HO-1 and NQO1,reduced the IL-6 release,while there has no significance when Nrf2 was blocked in CSE-induced NHBE cells.CONCLUSION Our results demonstrated that Wnt3a/β-catenin significantly balanced oxidative stress and attenuated inflammation reaction by promoting Nrf2 nuclear translocation and activity.