AIM： To investigate the effects of arginine （Arg）-enriched diets before sepsis and/or Arg-containing total parenteral nutrition （TPN） after sepsis or both on cytokine mRNA expression levels in splenocytes of rats...AIM： To investigate the effects of arginine （Arg）-enriched diets before sepsis and/or Arg-containing total parenteral nutrition （TPN） after sepsis or both on cytokine mRNA expression levels in splenocytes of rats with gut-derived sepsis. METHODS： Rats were assigned to four experimental groups. Groups 1 and 2 were fed with a semipurified diet, while groups 3 and 4 had part of the casein replaced by Arg which provided 2% of the total calories. After the rats were fed with these diets for 10 d, sepsis was induced by cecal ligation and puncture （CLP）, at the same time an internal jugular vein was cannulated. All rats were maintained on TPN for 3 d. Groups 1 and 3 were infused with conventional TPN, while groups 2 and 4 were supplemented with Arg which provided 2% of the total calories in the TPN solution. All rats were killed 3 d after CLP to examine their splenocyte subpopulation distribution and cytokine expression levels. RESULTS： Plasma interleukin （IL）-2, IL-4, tumor necrosis factor-α （TNF-α） and interferon （IFN-γ） were not detectable 3 d after CL.P. There were no differences in the distributions of CD45Ra＋, CD3＋, CD4＋, and CD8＋ cells in whole blood and splenocytes among the four groups. The splenocyte IL-2 mRNA expression in the Arg-supplemented groups was significantly higher than that in group 1. IL-4 mRNA expression in groups 3 and 4 was significantly higher than that in groups 1 and 2. The mRNA expression of IL-10 and IFN-γ was significantly higher in group 4 than in the other three groups. There was no difference in TNF-α mRNA expression among thefour groups CONCLUSION： The influence of Arg on the whole blood and splenic lymphocyte subpopulation distribution is not obvious. However, Arg administration, especially before and after CLP, significantly enhances the mRNA expression levels of Thl and Th2 cytokines in the spleen of rats with gut-derived sepsis.展开更多
Objective To study the significance of scavenger receptor class A(SR A)in mediating human peripheral blood monocyte to uptake oxidized low density lipoprotein(OxLDL) and promoting the atherosclerotic immuno patholo...Objective To study the significance of scavenger receptor class A(SR A)in mediating human peripheral blood monocyte to uptake oxidized low density lipoprotein(OxLDL) and promoting the atherosclerotic immuno pathological lesion in the local blood vessel. Methods With the Digoxenin labeled Oligonucleotide probes In situ Hybridization, this research investigated the effects of OxLDL on the mRNA expression of proinflammatory cytokines including MCP 1, bFGF, PDGF and IL 10 in the human peripheral blood monocyte and whether fucoidin, a peculiarly inhibitory ligand for SR A, would influence this process. Results Monocyte was significantly increased the mRNA expression of MCP 1, bFGF, PDGF and IL 10 in a dose dependent manner after incubating with OxLDL (10,15,20,25,30?mg·L -1 , respectively)for 24 hours( P < 0.001 ). Fucoidin(50,100,150,200,250?mg·mL -1 , respectively)completely inhibited OxLDL(20?mg·L -1 )from inducing monocyte the mRNA expression of above proinflammatory cytokines( P < 0.001 ). Conclusion OxLDL can stimulate human peripheral blood monocyte to give expression to proinflammatory cytokines mRNA in a dose dependent manner, while a peculiarly inhibitory ligand for SR A fucoidin has an obviously opposed role.展开更多
Background: Chemokines are small proteins that activate immune system in normal and pathological conditions. The induction of chemotaxis is a well-established role of chemokines. Moreover chemokines are important medi...Background: Chemokines are small proteins that activate immune system in normal and pathological conditions. The induction of chemotaxis is a well-established role of chemokines. Moreover chemokines are important mediators of angiogenesis, implantation of fetus, and maturation of immune cells. In human body many types of cells express chemokines and cytokines at level of gene and protein. In blood cells chemokine and chemokine receptors mRNA level is a one of crucial points of chemokine system condition. The aim of the study was to evaluate the relationship between plasma concentration of cyto- kines and chemokines/chemokine receptors mRNA level in blood of healthy volunteers. Results: Gene expression of eotaxin, eotaxin-2, IL-8, MIP-1α, MIP- 1β, RANTES, CCR1, CCR3, CCR5, CXCR1, and CXCR2 was measured in peripheral blood cells, as well as the concentration of IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, eotaxin, FGF-2, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, and VEGF was evaluated in the plasma of 19 healthy individuals. We studied rela- tionship between mRNA levels of chemokines/recaptors and cytokine concentration in blood of healthy volunteers. Conclusion: These data are allowed to assess chemokines impact in the cytokine regulation of healthy subjects. These results indicate that chemokines and their receptors is diverse and redundant system of immune reactivity in response to internal and external challenges.展开更多
The effects of recombinant galectins of male and female Hemonchus contortus （Hco-gal-m/f） on the mRNA levels of IL-1β, IL-2, IL-4, IL-6, interferon-γ（IFN-γ）, and tumor necrosis factor-γ （TNF-γ） of goat peri...The effects of recombinant galectins of male and female Hemonchus contortus （Hco-gal-m/f） on the mRNA levels of IL-1β, IL-2, IL-4, IL-6, interferon-γ（IFN-γ）, and tumor necrosis factor-γ （TNF-γ） of goat peripheral blood mononuclear cells （PBMCs） were examined in this study. Blood samples were collected from five randomly selected two-year-old healthy goats. PBMCs were separated and cultured in vitro with varying concentration galectins （Hco-gal-m/f） of 0, 10, 20, and 40 lag mL-L Semi-quantitative reverse transcription RT-PCR was employed to test the synthesis of mRNA. The results showed that the mRNA transcriptions of IL-1β, IL-2, IL-4, IL-6, IFN-γ, and TNF-γ in the PBMCs were inhibited by Hco-galm in a dose-dependent manner. Hco-gal-f inhibited mRNA synthesis of IL- 1β, IL-4, IFN-γ, and TNF-γ of the same cells in similar fashion. The findings suggested that the recombinant galectin proteins of H. contortus could decrease the transcription of cytokines in vitro.展开更多
Background: An accurate diagnosis of cause of acute renal graft dysfunction is crucial for the optimal management of transplant recipients. Currently available tests are either insensitive or nonspecific, or are invas...Background: An accurate diagnosis of cause of acute renal graft dysfunction is crucial for the optimal management of transplant recipients. Currently available tests are either insensitive or nonspecific, or are invasive, such as allograft biopsy. During last decade, attempts have been made in search of non invasive markers for the evaluation of cause of graft dysfunction. We studied a set of genes expressed on cytotoxic T Lymphocytes and those related to functioning of regulatory or helper T cells. Methods: We obtained 108 urine samples from 108 renal allograft recipients at the time of graft biopsy done for the evaluation of cause of graft dysfunction. RNA was extracted from urinary cells and messenger RNA (mRNA) encoding perforin, granzyme B (GB), FoxP3, CD3?, CXCR3, TGF-?, CTLA4, PI-9, IL-10, TNF?, T-bet and 18SrRNA measured with the use of quantitative real time polymerase chain reaction (RT-PCR). The levels of expression of genes were correlated with the biopsy findings and the results compared among different groups. Renal allograft biopsies at this institution are performed when there is unexplained rise in serum creatinine of >20% from the baseline value and reported according to Banff classification. SPSS v10.0 used for analy-sis.Results: The mRNA copy numbers of GB, Perforin, FoxP3, CD3, CXCR3, TGF-?, CTL A4, PI9, IL-10, TNF?, and T-bet were log transformed and mean (± SD) levels studied. The expression of all studied genes were compared between ‘nonspecific biopsy findings’ and other specific diagnoses. GB, Perforin, FoxP3, TGF-?, CD3?, CTLA4 CXCR3 and T-bet were higher in acute cellular rejection (ACR), whereas, TGF-? was also found higher in infection, and PI-9 in chronic allograft nephropathy (CAN) and borderline rejection group. Conclusion: Measurement of mRNA levels for genes like GB, Perforin, FoxP3, TGF-β, CD3?, CTLA4, CXCR3 and T-bet in urine samples offers a non invasive means of diag-nosing cause of graft dysfunction.展开更多
In order to analyze the mechanism of immunomodulation by LPS on murine peritoneal suppressor macrophages, we have, using RNase protection assay,checked the changes of mRNA expression pattern of several cytokine genes ...In order to analyze the mechanism of immunomodulation by LPS on murine peritoneal suppressor macrophages, we have, using RNase protection assay,checked the changes of mRNA expression pattern of several cytokine genes during the immuno-modulation.It has been found that, after treating peritoneal suppressor macrophages with LPS, mRNAs of IL-12 p35, IL-12 p40,IL-6 and IFN-γ are newly appeared, while those of IL-1α, IL-1β and IL-1Ra are increased and those of other cytokines, like TGF-β1 and MIF are not changed at all.It seems certain that those cytokines, whose expression is increased by LPS stimulation, may be responsible for the functional changes of suppressor macrophages during immuno-modulation. Among these changes, the appearance of IL-12 mRNA may play a critical role, and, in this regard, the synergetic effect between IFN-γ and LPS on the increase of IL-12 p35 and IL-12 p40 mRNA expression is an interesting finding.展开更多
AIM: To investigate the role of cytokine gene expression inorgan damage at different tissue sites during sepsis.METHODS: Male NIH mice were subjected to cecal ligationand puncture (CLP) or sham operetion ( Sham ). Pro...AIM: To investigate the role of cytokine gene expression inorgan damage at different tissue sites during sepsis.METHODS: Male NIH mice were subjected to cecal ligationand puncture (CLP) or sham operetion ( Sham ). Pro-inflammatory cytokine (TNFα, IL-1β and IL-6) and anti-inflammatory cytokine (IL-4) gene expression in the liverand lung tissue were assessed by RT-PCR. The permeabilityof microvascular and water content in the lungs and liverwere also examined.RESULTS: Significant increase in TNFα, IL-1β and IL-6 geneexpression was observed at 3 and 12 h after CLP both in theliver and lungs ( P＜ 0.01). The level of IL-4 gene expressionwas not changed after CLP in the lungs, but increased at 12h after CLP ( P ＜ 0.01) in the liver tissue. Both the liver andlungs showed a significant increase in microcirculatorypermeability at 12 h after CLP (P＜ 0.01), and the increasein the lungs was higher than that in the liver. The watermaes fractions in the liver ( P＜ 0.05) and lungs ( P＜ 0.01)were increased after CLP, and the increase in the lungshappened earlier and more severely than that in the liver.CONCLUSION: The inflammatory response in the liver andlungs wes different during sepsis. At the early stage ofsepsis, pro-inflammatory reaction dominates both in theliver and lungs. But at the later stage of sepsis, induction ofcompensatory anti-inflammatory response was seen in theliver but not in the lungs. This difference in situ activity maycontribute to the different vulnerability of organ damageduring sepsis. The strategy of systemic administration ofanti-inflammatory drugs to sepsis should be reconsidered.展开更多
BACKGROUND Generalized anxiety disorder(GAD)is a relatively common mental disorder.Recently,inflammation,an important factor for the development of depression,has attracted increasing attention.Several studies have sh...BACKGROUND Generalized anxiety disorder(GAD)is a relatively common mental disorder.Recently,inflammation,an important factor for the development of depression,has attracted increasing attention.Several studies have shown that inflammatory cytokines can affect the pathophysiological processes of several nervous system diseases.We hypothesized that there is a correlation between the levels of lipopolysaccharide(LPS)-stimulated inflammatory cytokines and the clinical symptoms of GAD.AIM To investigate the predictive effect of LPS-stimulated inflammatory cytokines on symptoms of GAD.METHODS This was a cross-sectional study in which 89 patients with GAD diagnosed at The First Hospital of Hebei Medical University from January 2022 to December 2022 and 70 individuals without anxiety and depression(controls)during the same period were included.Fasting venous blood was collected from all the subjects in heparin tubes,and another 3 ml of blood was supplemented with LPS(10 ng/ml).The plasma levels of 12 cytokines[Interleukin(IL)-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,tumor necrosis factor(TNF)-α,interferon(IFN)-γ,IL-17A,IL-12p70,and IFN-α]were detected.RESULTS Post-LPS stimulation,the levels of IL-1β,IL-6,IL-8,IL-10,and TNF-αin both the control and GAD groups were significantly elevated above those in the nonstimulated groups,with IL-6 and IL-8 showing marked increases.Increases in IL-8 and TNF-αwere statistically significant in the GAD group(P<0.05).IL-1β,IL-6,IL-8,IL-10,and TNF-αwere found to be significantly correlated with Hamilton Anxiety Rating Scale(HAMA)scores(P<0.05).A negative correlation was observed between IL-10 levels and HAMA scores.Further analysis revealed that TNF-αwas associated with mental anxiety,whereas IL-1β,IL-8,and IL-10 were associated with physical anxiety symptoms,with IL-10 showing a negative correlation with physical anxiety.IL-6 was associated with both mental and physical aspects of anxiety.CONCLUSION The physical symptoms of GAD are related to inflammatory factors.IL-1β,IL-8,IL-10,and TNF-a can be used as predictors of physical or mental anxiety in patients with GAD.展开更多
AIM: To investigate the effects of glutamine (GLN)-enriched diets before and GLN-containing total parenteral nutrition (TPN) after sepsis or both on the secretion of cytokines and their mRNA expression levels in splen...AIM: To investigate the effects of glutamine (GLN)-enriched diets before and GLN-containing total parenteral nutrition (TPN) after sepsis or both on the secretion of cytokines and their mRNA expression levels in splenocytes of rats with septic peritonitis.METHODS: Rats were assigned to a control group and 4experimental groups. The control group and experimental groups 1 and 2 were fed a semipurified diet, while experimental groups 3 and 4 had part of the casein replaced by GLN which provided 25% of the total nitrogen.After rats were fed with these diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP), whereas the control group underwent a sham operation, at the same time, an internal jugular vein was cannulated. All rats were maintained on TPN for 3 d. The control group and experimental groups 1 and 3 were infused with conventional TPN, while the TPN in experimental groups 2 and 4 was supplemented with GLN, providing 25% of the total nitrogen in the TPN solution. All rats were kiued 3 d after sham operation or CLP to examine their splenocyte subpopulation distribution and cytokine expression levels.RESULTS: Most cytokines could not be detected in plasma except for IL-10. No difference in plasma IL-10 was observed among the 5 groups. The IL-2, IL-4, IL-10, and TNF-α mRNA expression levels in splenocytes were significantly higher in experimental groups 2 and 4 than in the control group and group 1. The mRNA expression of IFN-γ was significantly higher in the GLN-supplemented groups than in the control group and experimental group 1. The proportion of CD45Ra+ was increased, while those of CD3+ and CD4+ were decreased in experimental group 1 after CLP was performed. There were no differences in spleen CD3+ lymphocyte distributions between the control and GLN-supplemented groups.CONCLUSION:GLN supplementation can maintain Tlymphocyte populations in the spleen and significantly enhance the mRNA expression levels of Th1 and Th2cytokines and TNF-α in the spleen of rats with septic peritonitis.展开更多
Cardiovascular disease(CVD)has become the leading cause of death globally,imposing significant health and economic burdens.Among these,myocardial infarction(MI)is a predominant cause of mortality.Several animal studie...Cardiovascular disease(CVD)has become the leading cause of death globally,imposing significant health and economic burdens.Among these,myocardial infarction(MI)is a predominant cause of mortality.Several animal studies have shown that cytokines participate in cardiac regeneration and repair by modulating cellular proliferation,differentiation,and apoptosis post-MI.Here,we explored the crucial role of cytokines in cardiac regeneration and repair processes in experimental animal models,detailing how cytokines modulate cellular mechanisms involved in repairing cardiac tissue post myocardial infarction(MI).Specifically,it highlights the activation of cardiac stem cells and progenitors,the regulation of inflammatory responses to prevent excessive damage,and the involvement in matrix remodeling to ensure functional integrity of the heart.This comprehensive examination underscores the therapeutic potential of enhancing cytokine secretion to mitigate adverse effects and promote recovery following MI,offering insights into possible interventions that could improve patient outcomes in clinical settings.展开更多
Objective:To explore the effect of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-18,IL-1β,and aging on the expression of P2X7receptor(P2X7R)m RNA in the brains of mice with lipopolysaccharide(LPS)treatment.Me...Objective:To explore the effect of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-18,IL-1β,and aging on the expression of P2X7receptor(P2X7R)m RNA in the brains of mice with lipopolysaccharide(LPS)treatment.Methods:Young(4 months old)and aged(18 months old)male C57BL/6 mice were randomly divided into 5 groups(n=7).All of the mice were injected intraperitoneally with LPS(0.5 mg/kg).After 0,3,24,48,and 72 h,the m RNA expressions of TNF-α,IL-6,IL-18,IL-1β,and P2X7R in mice's brains were determined by q PCR.Results:In brains of young mice,the highest expressions of IL-6,IL-18 and IL-1βwere found at3 h,but for TNF-αand P2X7R,the highest expressions were found at 24 h.For the aged mice,the expressions of TNF-α,IL-6,IL-1β,and P2X7R reached the highest level at 3 h,but IL-18reached the highest level at 24 h.Aged mice showed significantly higher level of TNF-αat 0,3,48,and 72 h than young mice.The similar results were observed for P2X7R at 0,3 and72 h in aged mice.Conclusion:The m RNA expression of inflammatory cytokines and P2X7R in the brains of mice were consistent with the same time points after LPS treatment.Furthermore,they were higher in aged mice compared with young mice.This result suggested that P2X7R may be involved in the development of brain aging and relevant diseases of mice by regulating the expression of inflammatory cytokines.展开更多
After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune...After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune response as a treatment for spinal cord injury.Although much research has been performed analyzing the complex inflammatory process following spinal cord injury,there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation.The objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury,identify sexual dimorphisms in terms of cytokine levels,and determine local cytokines that significantly change based on the severity of spinal cord injury.Rats were inflicted with either a mild contusion,moderate contusion,severe contusion,or complete transection,7 mm of spinal cord centered on the injury was harvested at varying times post-injury,and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex assay.Results demonstrated pro-inflammatory cytokines including tumor necrosis factorα,interleukin-1β,and interleukin-6 were all upregulated after spinal cord injury,but returned to uninjured levels within approximately 24 hours post-injury,while chemokines including monocyte chemoattractant protein-1 remained upregulated for days post-injury.In contrast,several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days post-injury.After spinal cord injury,tissue inhibitor of metalloproteinase-1,which specifically affects astrocytes involved in glial scar development,increased more than all other cytokines tested,reaching 26.9-fold higher than uninjured rats.After a mild injury,11 cytokines demonstrated sexual dimorphisms;however,after a severe contusion only leptin levels were different between female and male rats.In conclusion,pro-inflammatory cytokines initiate the inflammatory process and return to baseline within hours post-injury,chemokines continue to recruit immune cells for days post-injury,while anti-inflammatory cytokines are downregulated by a week post-injury,and sexual dimorphisms observed after mild injury subsided with more severe injuries.Results from this work define critical chemokines that influence immune cell infiltration and important cytokines involved in glial scar development after spinal cord injury,which are essential for researchers developing treatments targeting secondary damage after spinal cord injury.展开更多
This editorial refers to the article“Comparative analysis of Nε-carboxymethyllysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients”,published in the recent issue of the World...This editorial refers to the article“Comparative analysis of Nε-carboxymethyllysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients”,published in the recent issue of the World Journal of Diabetes 2023 is based on glucose metabolism,advanced glycation end products(AGEs),inflammation and adiposity on diabetes and coronary artery disease(CAD).This study has included CAD patients who were stratified according to glycosylated hemoglobin higher than 6.5 and sex-matched.A higher prevalence of hypertension,dyslipidemia,and non-vegetarian diet were found in the diabetic group.These risk factors might influence body weight and adiposity and explain the increment of the left atrium.Although this data was not supported by the study.The diet can also explain the non-enzymatic reactions on lipids,proteins,or nucleic acids and consequently an increment of AGEs.These molecules can emit fluorescence.However,one of the non-fluorescent and most abundant AGEs is Nε-carboxymethyl-lysine(CML).Its association with coronary artery stenosis and severity in the diabetic group might suggest its role as a player in CAD progression.Thus,CML,after binding with its receptor(RAGE),can induce calcification cascade through reactive oxygen species and mitogen-activated protein kinase.Moreover,this interaction AGE-RAGE can cause activation of the transcription nuclear factor-kb and induce inflammatory cytokines.It might explain the relationship between CML and pro-inflammatory cytokines in diabetic and CAD patients.Although this is a population from one center,the determination of CML and inflammatory cytokines might improve the diagnosis of severe and progressive CAD.Future and comparative studies among glycosylated hemoglobin,CML,and other AGE levels according to diagnosis and prognosis value might modify the clinical practice.Although these molecules are irreversible,they can act through a specific receptor inducing a signal transduction that might be modulated by inhibitors,antibodies,or siRNA.Further mechanistic studies might improve the development of future preventive therapies for diabetic patients.展开更多
基金Supported by a research grant from the National Science Council, Taipei, Taiwan, China. No. NSC 92-2320-B-038-029
文摘AIM： To investigate the effects of arginine （Arg）-enriched diets before sepsis and/or Arg-containing total parenteral nutrition （TPN） after sepsis or both on cytokine mRNA expression levels in splenocytes of rats with gut-derived sepsis. METHODS： Rats were assigned to four experimental groups. Groups 1 and 2 were fed with a semipurified diet, while groups 3 and 4 had part of the casein replaced by Arg which provided 2% of the total calories. After the rats were fed with these diets for 10 d, sepsis was induced by cecal ligation and puncture （CLP）, at the same time an internal jugular vein was cannulated. All rats were maintained on TPN for 3 d. Groups 1 and 3 were infused with conventional TPN, while groups 2 and 4 were supplemented with Arg which provided 2% of the total calories in the TPN solution. All rats were killed 3 d after CLP to examine their splenocyte subpopulation distribution and cytokine expression levels. RESULTS： Plasma interleukin （IL）-2, IL-4, tumor necrosis factor-α （TNF-α） and interferon （IFN-γ） were not detectable 3 d after CL.P. There were no differences in the distributions of CD45Ra＋, CD3＋, CD4＋, and CD8＋ cells in whole blood and splenocytes among the four groups. The splenocyte IL-2 mRNA expression in the Arg-supplemented groups was significantly higher than that in group 1. IL-4 mRNA expression in groups 3 and 4 was significantly higher than that in groups 1 and 2. The mRNA expression of IL-10 and IFN-γ was significantly higher in group 4 than in the other three groups. There was no difference in TNF-α mRNA expression among thefour groups CONCLUSION： The influence of Arg on the whole blood and splenic lymphocyte subpopulation distribution is not obvious. However, Arg administration, especially before and after CLP, significantly enhances the mRNA expression levels of Thl and Th2 cytokines in the spleen of rats with gut-derived sepsis.
文摘Objective To study the significance of scavenger receptor class A(SR A)in mediating human peripheral blood monocyte to uptake oxidized low density lipoprotein(OxLDL) and promoting the atherosclerotic immuno pathological lesion in the local blood vessel. Methods With the Digoxenin labeled Oligonucleotide probes In situ Hybridization, this research investigated the effects of OxLDL on the mRNA expression of proinflammatory cytokines including MCP 1, bFGF, PDGF and IL 10 in the human peripheral blood monocyte and whether fucoidin, a peculiarly inhibitory ligand for SR A, would influence this process. Results Monocyte was significantly increased the mRNA expression of MCP 1, bFGF, PDGF and IL 10 in a dose dependent manner after incubating with OxLDL (10,15,20,25,30?mg·L -1 , respectively)for 24 hours( P < 0.001 ). Fucoidin(50,100,150,200,250?mg·mL -1 , respectively)completely inhibited OxLDL(20?mg·L -1 )from inducing monocyte the mRNA expression of above proinflammatory cytokines( P < 0.001 ). Conclusion OxLDL can stimulate human peripheral blood monocyte to give expression to proinflammatory cytokines mRNA in a dose dependent manner, while a peculiarly inhibitory ligand for SR A fucoidin has an obviously opposed role.
文摘Background: Chemokines are small proteins that activate immune system in normal and pathological conditions. The induction of chemotaxis is a well-established role of chemokines. Moreover chemokines are important mediators of angiogenesis, implantation of fetus, and maturation of immune cells. In human body many types of cells express chemokines and cytokines at level of gene and protein. In blood cells chemokine and chemokine receptors mRNA level is a one of crucial points of chemokine system condition. The aim of the study was to evaluate the relationship between plasma concentration of cyto- kines and chemokines/chemokine receptors mRNA level in blood of healthy volunteers. Results: Gene expression of eotaxin, eotaxin-2, IL-8, MIP-1α, MIP- 1β, RANTES, CCR1, CCR3, CCR5, CXCR1, and CXCR2 was measured in peripheral blood cells, as well as the concentration of IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, eotaxin, FGF-2, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, and VEGF was evaluated in the plasma of 19 healthy individuals. We studied rela- tionship between mRNA levels of chemokines/recaptors and cytokine concentration in blood of healthy volunteers. Conclusion: These data are allowed to assess chemokines impact in the cytokine regulation of healthy subjects. These results indicate that chemokines and their receptors is diverse and redundant system of immune reactivity in response to internal and external challenges.
基金the National Natural Science Foundation of China （30071078）.
文摘The effects of recombinant galectins of male and female Hemonchus contortus （Hco-gal-m/f） on the mRNA levels of IL-1β, IL-2, IL-4, IL-6, interferon-γ（IFN-γ）, and tumor necrosis factor-γ （TNF-γ） of goat peripheral blood mononuclear cells （PBMCs） were examined in this study. Blood samples were collected from five randomly selected two-year-old healthy goats. PBMCs were separated and cultured in vitro with varying concentration galectins （Hco-gal-m/f） of 0, 10, 20, and 40 lag mL-L Semi-quantitative reverse transcription RT-PCR was employed to test the synthesis of mRNA. The results showed that the mRNA transcriptions of IL-1β, IL-2, IL-4, IL-6, IFN-γ, and TNF-γ in the PBMCs were inhibited by Hco-galm in a dose-dependent manner. Hco-gal-f inhibited mRNA synthesis of IL- 1β, IL-4, IFN-γ, and TNF-γ of the same cells in similar fashion. The findings suggested that the recombinant galectin proteins of H. contortus could decrease the transcription of cytokines in vitro.
文摘Background: An accurate diagnosis of cause of acute renal graft dysfunction is crucial for the optimal management of transplant recipients. Currently available tests are either insensitive or nonspecific, or are invasive, such as allograft biopsy. During last decade, attempts have been made in search of non invasive markers for the evaluation of cause of graft dysfunction. We studied a set of genes expressed on cytotoxic T Lymphocytes and those related to functioning of regulatory or helper T cells. Methods: We obtained 108 urine samples from 108 renal allograft recipients at the time of graft biopsy done for the evaluation of cause of graft dysfunction. RNA was extracted from urinary cells and messenger RNA (mRNA) encoding perforin, granzyme B (GB), FoxP3, CD3?, CXCR3, TGF-?, CTLA4, PI-9, IL-10, TNF?, T-bet and 18SrRNA measured with the use of quantitative real time polymerase chain reaction (RT-PCR). The levels of expression of genes were correlated with the biopsy findings and the results compared among different groups. Renal allograft biopsies at this institution are performed when there is unexplained rise in serum creatinine of >20% from the baseline value and reported according to Banff classification. SPSS v10.0 used for analy-sis.Results: The mRNA copy numbers of GB, Perforin, FoxP3, CD3, CXCR3, TGF-?, CTL A4, PI9, IL-10, TNF?, and T-bet were log transformed and mean (± SD) levels studied. The expression of all studied genes were compared between ‘nonspecific biopsy findings’ and other specific diagnoses. GB, Perforin, FoxP3, TGF-?, CD3?, CTLA4 CXCR3 and T-bet were higher in acute cellular rejection (ACR), whereas, TGF-? was also found higher in infection, and PI-9 in chronic allograft nephropathy (CAN) and borderline rejection group. Conclusion: Measurement of mRNA levels for genes like GB, Perforin, FoxP3, TGF-β, CD3?, CTLA4, CXCR3 and T-bet in urine samples offers a non invasive means of diag-nosing cause of graft dysfunction.
文摘In order to analyze the mechanism of immunomodulation by LPS on murine peritoneal suppressor macrophages, we have, using RNase protection assay,checked the changes of mRNA expression pattern of several cytokine genes during the immuno-modulation.It has been found that, after treating peritoneal suppressor macrophages with LPS, mRNAs of IL-12 p35, IL-12 p40,IL-6 and IFN-γ are newly appeared, while those of IL-1α, IL-1β and IL-1Ra are increased and those of other cytokines, like TGF-β1 and MIF are not changed at all.It seems certain that those cytokines, whose expression is increased by LPS stimulation, may be responsible for the functional changes of suppressor macrophages during immuno-modulation. Among these changes, the appearance of IL-12 mRNA may play a critical role, and, in this regard, the synergetic effect between IFN-γ and LPS on the increase of IL-12 p35 and IL-12 p40 mRNA expression is an interesting finding.
基金the National Natural Science Foundation of China,No.39870796
文摘AIM: To investigate the role of cytokine gene expression inorgan damage at different tissue sites during sepsis.METHODS: Male NIH mice were subjected to cecal ligationand puncture (CLP) or sham operetion ( Sham ). Pro-inflammatory cytokine (TNFα, IL-1β and IL-6) and anti-inflammatory cytokine (IL-4) gene expression in the liverand lung tissue were assessed by RT-PCR. The permeabilityof microvascular and water content in the lungs and liverwere also examined.RESULTS: Significant increase in TNFα, IL-1β and IL-6 geneexpression was observed at 3 and 12 h after CLP both in theliver and lungs ( P＜ 0.01). The level of IL-4 gene expressionwas not changed after CLP in the lungs, but increased at 12h after CLP ( P ＜ 0.01) in the liver tissue. Both the liver andlungs showed a significant increase in microcirculatorypermeability at 12 h after CLP (P＜ 0.01), and the increasein the lungs was higher than that in the liver. The watermaes fractions in the liver ( P＜ 0.05) and lungs ( P＜ 0.01)were increased after CLP, and the increase in the lungshappened earlier and more severely than that in the liver.CONCLUSION: The inflammatory response in the liver andlungs wes different during sepsis. At the early stage ofsepsis, pro-inflammatory reaction dominates both in theliver and lungs. But at the later stage of sepsis, induction ofcompensatory anti-inflammatory response was seen in theliver but not in the lungs. This difference in situ activity maycontribute to the different vulnerability of organ damageduring sepsis. The strategy of systemic administration ofanti-inflammatory drugs to sepsis should be reconsidered.
基金The 2023 Scientific Research Fund Project of Hebei Provincial Health and Family Planning Commission,No.20231081The"Spark"Youth Research Project,The First Hospital of Hebei Medical University,No.XH202302.
文摘BACKGROUND Generalized anxiety disorder(GAD)is a relatively common mental disorder.Recently,inflammation,an important factor for the development of depression,has attracted increasing attention.Several studies have shown that inflammatory cytokines can affect the pathophysiological processes of several nervous system diseases.We hypothesized that there is a correlation between the levels of lipopolysaccharide(LPS)-stimulated inflammatory cytokines and the clinical symptoms of GAD.AIM To investigate the predictive effect of LPS-stimulated inflammatory cytokines on symptoms of GAD.METHODS This was a cross-sectional study in which 89 patients with GAD diagnosed at The First Hospital of Hebei Medical University from January 2022 to December 2022 and 70 individuals without anxiety and depression(controls)during the same period were included.Fasting venous blood was collected from all the subjects in heparin tubes,and another 3 ml of blood was supplemented with LPS(10 ng/ml).The plasma levels of 12 cytokines[Interleukin(IL)-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,tumor necrosis factor(TNF)-α,interferon(IFN)-γ,IL-17A,IL-12p70,and IFN-α]were detected.RESULTS Post-LPS stimulation,the levels of IL-1β,IL-6,IL-8,IL-10,and TNF-αin both the control and GAD groups were significantly elevated above those in the nonstimulated groups,with IL-6 and IL-8 showing marked increases.Increases in IL-8 and TNF-αwere statistically significant in the GAD group(P<0.05).IL-1β,IL-6,IL-8,IL-10,and TNF-αwere found to be significantly correlated with Hamilton Anxiety Rating Scale(HAMA)scores(P<0.05).A negative correlation was observed between IL-10 levels and HAMA scores.Further analysis revealed that TNF-αwas associated with mental anxiety,whereas IL-1β,IL-8,and IL-10 were associated with physical anxiety symptoms,with IL-10 showing a negative correlation with physical anxiety.IL-6 was associated with both mental and physical aspects of anxiety.CONCLUSION The physical symptoms of GAD are related to inflammatory factors.IL-1β,IL-8,IL-10,and TNF-a can be used as predictors of physical or mental anxiety in patients with GAD.
基金Supported by the Research Grant from National Science Council, Taipei, Taiwan, No. NSC 92-2314-B-002-278
文摘AIM: To investigate the effects of glutamine (GLN)-enriched diets before and GLN-containing total parenteral nutrition (TPN) after sepsis or both on the secretion of cytokines and their mRNA expression levels in splenocytes of rats with septic peritonitis.METHODS: Rats were assigned to a control group and 4experimental groups. The control group and experimental groups 1 and 2 were fed a semipurified diet, while experimental groups 3 and 4 had part of the casein replaced by GLN which provided 25% of the total nitrogen.After rats were fed with these diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP), whereas the control group underwent a sham operation, at the same time, an internal jugular vein was cannulated. All rats were maintained on TPN for 3 d. The control group and experimental groups 1 and 3 were infused with conventional TPN, while the TPN in experimental groups 2 and 4 was supplemented with GLN, providing 25% of the total nitrogen in the TPN solution. All rats were kiued 3 d after sham operation or CLP to examine their splenocyte subpopulation distribution and cytokine expression levels.RESULTS: Most cytokines could not be detected in plasma except for IL-10. No difference in plasma IL-10 was observed among the 5 groups. The IL-2, IL-4, IL-10, and TNF-α mRNA expression levels in splenocytes were significantly higher in experimental groups 2 and 4 than in the control group and group 1. The mRNA expression of IFN-γ was significantly higher in the GLN-supplemented groups than in the control group and experimental group 1. The proportion of CD45Ra+ was increased, while those of CD3+ and CD4+ were decreased in experimental group 1 after CLP was performed. There were no differences in spleen CD3+ lymphocyte distributions between the control and GLN-supplemented groups.CONCLUSION:GLN supplementation can maintain Tlymphocyte populations in the spleen and significantly enhance the mRNA expression levels of Th1 and Th2cytokines and TNF-α in the spleen of rats with septic peritonitis.
基金supported by the Henan Medical Science and Technology Joint Building Program(No.LHGJ20230283)the Medical Science and Technology Research Project of Henan Province(No.SBGJ202103079).
文摘Cardiovascular disease(CVD)has become the leading cause of death globally,imposing significant health and economic burdens.Among these,myocardial infarction(MI)is a predominant cause of mortality.Several animal studies have shown that cytokines participate in cardiac regeneration and repair by modulating cellular proliferation,differentiation,and apoptosis post-MI.Here,we explored the crucial role of cytokines in cardiac regeneration and repair processes in experimental animal models,detailing how cytokines modulate cellular mechanisms involved in repairing cardiac tissue post myocardial infarction(MI).Specifically,it highlights the activation of cardiac stem cells and progenitors,the regulation of inflammatory responses to prevent excessive damage,and the involvement in matrix remodeling to ensure functional integrity of the heart.This comprehensive examination underscores the therapeutic potential of enhancing cytokine secretion to mitigate adverse effects and promote recovery following MI,offering insights into possible interventions that could improve patient outcomes in clinical settings.
基金supported by grants from National Natural Science Foundation of China(No.81170314,No. 81360421,No. 81560524)China Postdoctoral Science Foundation (No.2013M540686,No.2014T70839)Guangxi Natural Science Foundation(No.2012GXNSFBA053109)
文摘Objective:To explore the effect of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-18,IL-1β,and aging on the expression of P2X7receptor(P2X7R)m RNA in the brains of mice with lipopolysaccharide(LPS)treatment.Methods:Young(4 months old)and aged(18 months old)male C57BL/6 mice were randomly divided into 5 groups(n=7).All of the mice were injected intraperitoneally with LPS(0.5 mg/kg).After 0,3,24,48,and 72 h,the m RNA expressions of TNF-α,IL-6,IL-18,IL-1β,and P2X7R in mice's brains were determined by q PCR.Results:In brains of young mice,the highest expressions of IL-6,IL-18 and IL-1βwere found at3 h,but for TNF-αand P2X7R,the highest expressions were found at 24 h.For the aged mice,the expressions of TNF-α,IL-6,IL-1β,and P2X7R reached the highest level at 3 h,but IL-18reached the highest level at 24 h.Aged mice showed significantly higher level of TNF-αat 0,3,48,and 72 h than young mice.The similar results were observed for P2X7R at 0,3 and72 h in aged mice.Conclusion:The m RNA expression of inflammatory cytokines and P2X7R in the brains of mice were consistent with the same time points after LPS treatment.Furthermore,they were higher in aged mice compared with young mice.This result suggested that P2X7R may be involved in the development of brain aging and relevant diseases of mice by regulating the expression of inflammatory cytokines.
基金supported by the National Institutes of HealthNo.R56 NS117935(to ASH and WLM)+1 种基金funded by Institutional Clinical and Translational Science AwardNo.UL1 TR002373。
文摘After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune response as a treatment for spinal cord injury.Although much research has been performed analyzing the complex inflammatory process following spinal cord injury,there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation.The objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury,identify sexual dimorphisms in terms of cytokine levels,and determine local cytokines that significantly change based on the severity of spinal cord injury.Rats were inflicted with either a mild contusion,moderate contusion,severe contusion,or complete transection,7 mm of spinal cord centered on the injury was harvested at varying times post-injury,and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex assay.Results demonstrated pro-inflammatory cytokines including tumor necrosis factorα,interleukin-1β,and interleukin-6 were all upregulated after spinal cord injury,but returned to uninjured levels within approximately 24 hours post-injury,while chemokines including monocyte chemoattractant protein-1 remained upregulated for days post-injury.In contrast,several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days post-injury.After spinal cord injury,tissue inhibitor of metalloproteinase-1,which specifically affects astrocytes involved in glial scar development,increased more than all other cytokines tested,reaching 26.9-fold higher than uninjured rats.After a mild injury,11 cytokines demonstrated sexual dimorphisms;however,after a severe contusion only leptin levels were different between female and male rats.In conclusion,pro-inflammatory cytokines initiate the inflammatory process and return to baseline within hours post-injury,chemokines continue to recruit immune cells for days post-injury,while anti-inflammatory cytokines are downregulated by a week post-injury,and sexual dimorphisms observed after mild injury subsided with more severe injuries.Results from this work define critical chemokines that influence immune cell infiltration and important cytokines involved in glial scar development after spinal cord injury,which are essential for researchers developing treatments targeting secondary damage after spinal cord injury.
文摘This editorial refers to the article“Comparative analysis of Nε-carboxymethyllysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients”,published in the recent issue of the World Journal of Diabetes 2023 is based on glucose metabolism,advanced glycation end products(AGEs),inflammation and adiposity on diabetes and coronary artery disease(CAD).This study has included CAD patients who were stratified according to glycosylated hemoglobin higher than 6.5 and sex-matched.A higher prevalence of hypertension,dyslipidemia,and non-vegetarian diet were found in the diabetic group.These risk factors might influence body weight and adiposity and explain the increment of the left atrium.Although this data was not supported by the study.The diet can also explain the non-enzymatic reactions on lipids,proteins,or nucleic acids and consequently an increment of AGEs.These molecules can emit fluorescence.However,one of the non-fluorescent and most abundant AGEs is Nε-carboxymethyl-lysine(CML).Its association with coronary artery stenosis and severity in the diabetic group might suggest its role as a player in CAD progression.Thus,CML,after binding with its receptor(RAGE),can induce calcification cascade through reactive oxygen species and mitogen-activated protein kinase.Moreover,this interaction AGE-RAGE can cause activation of the transcription nuclear factor-kb and induce inflammatory cytokines.It might explain the relationship between CML and pro-inflammatory cytokines in diabetic and CAD patients.Although this is a population from one center,the determination of CML and inflammatory cytokines might improve the diagnosis of severe and progressive CAD.Future and comparative studies among glycosylated hemoglobin,CML,and other AGE levels according to diagnosis and prognosis value might modify the clinical practice.Although these molecules are irreversible,they can act through a specific receptor inducing a signal transduction that might be modulated by inhibitors,antibodies,or siRNA.Further mechanistic studies might improve the development of future preventive therapies for diabetic patients.
