BACKGROUND Interleukin 10 receptor alpha subunit(IL10RA)dysfunction is the main cause of very early-onset inflammatory bowel disease(VEO-IBD)in East Asians.AIM To identify disease-causing gene mutations in four patien...BACKGROUND Interleukin 10 receptor alpha subunit(IL10RA)dysfunction is the main cause of very early-onset inflammatory bowel disease(VEO-IBD)in East Asians.AIM To identify disease-causing gene mutations in four patients with VEO-IBD and verify functional changes related to the disease-causing mutations.METHODS From May 2016 to September 2020,four young patients with clinically diagnosed VEO-IBD were recruited.Before hospitalization,using targeted gene panel sequencing and trio-whole-exome sequencing(WES),three patients were found to harbor a IL10RA mutation(c.301C>T,p.R101W in one patient;c.537G>A,p.T179T in two patients),but WES results of the fourth patient were not conclusive.We performed whole-genome sequencing(WGS)on patients A and B and reanalyzed the data from patients C and D.Peripheral blood mononuclear cells(PBMCs)from patient D were isolated and stimulated with lipopolysaccharide(LPS),interleukin 10(IL-10),and LPS+IL-10.Serum IL-10 levels in four patients and tumor necrosis factor-α(TNF-α)in the cell supernatant were determined by enzyme-linked immunosorbent assay.Phosphorylation of signal transducer and activator of transcription 3(STAT3)at Tyr705 and Ser727 in PBMCs was determined by western blot analysis.RESULTS The four children in our study consisted of two males and two females.The age at disease onset ranged from 18 d to 9 mo.After hospitalization,a novel 333-bp deletion encompassing exon 1 of IL10RA was found in patients A and B using WGS and was found in patients C and D after reanalysis of their WES data.Patient D was homozygous for the 333 bp deletion.All four patients had elevated serum IL-10 levels.In vitro,IL-10-stimulated PBMCs from patient D failed to induce STAT3 phosphorylation at Tyr705 and only minimally suppressed TNF-αproduction induced by LPS.Phosphorylation at Ser727 in PBMCs was not affected by LPS or LPS+IL-10 in both healthy subjects and in patient D.CONCLUSION WGS revealed a novel 333-bp deletion of IL10RA in four patients with VEO-IBD,whereas the WES results were inconclusive.展开更多
OBJECTIVES: To evaluate the behavior of serum interleukin 10 (IL-10) in patients with acutepancreatitis and to explore the relationship between this cytokine and the severity of the disease.METHODS: In 45 patients wit...OBJECTIVES: To evaluate the behavior of serum interleukin 10 (IL-10) in patients with acutepancreatitis and to explore the relationship between this cytokine and the severity of the disease.METHODS: In 45 patients with acute pancreatitis, the serum concentrations of IL-10 was determinedon days 1, 2, 3, 4, 5 after admission. Twelve healthy subjects were also studied as controls. Thesesubjects were tested using a commercial ELISA kit. The severity of pancreatitis was determined accordingto APACHE Ⅱ score and Balthazar CT criteria.RESULTS: Healthy subjects had no detectable serum levels of IL-10. In acute pancreatitis patients,the serum IL-10 levels were increased on the first day after the onset of the disease and then progressivelydecreased in the following days. On the first day after the onset of acute pancreatitis, the serum levelsof IL-10 in patients with mild acute pancreatitis were significantly higher than in those with severe acutepancreatitis. In the following days, however, no statistically significant difference was observed betweenthe two groups.CONCLUSIONS: Serum IL-10 concentration reflects the severity of acute pancreatitis. IL-10 is a usefulvariable for early prediction of the prognosis of acute pancreatitis. The low values of serum IL-10 inpatients with severe acute pancreatitis suggests that there may be altered down-regulation of immunesystem response. An enhanced release of IL-10 may be a method for early treatment of acute pancreatitis.展开更多
Objective. To study the effect of interleukin 10 (IL- 10) on the angiotensin II (AngII) stimulated rat VSMC proliferation and collagen secretion, and furthermore, explore its mechanism. Methods. On cultured VSMC of ra...Objective. To study the effect of interleukin 10 (IL- 10) on the angiotensin II (AngII) stimulated rat VSMC proliferation and collagen secretion, and furthermore, explore its mechanism. Methods. On cultured VSMC of rat, 3H- thymine (3H- TdR) and 3H- proline incorporations were used to evaluate the DNA and collagen synthesis, respectively. Western blot and immunoprecipitation were applied to assay the expression and activity of focal adhesion kinase (FAK), respectively. Results. IL- 10 (10－ 8～ 10－ 10g/ml) inhibited the increase of 3H- TdR and 3H- proline incorporation as well as FAK activity, which was induced by 10－ 7mol/L AngII (P< 0.05 or P< 0.01). IL- 10 also obviously downregulated the synthesis and secretion of collagen by AngII stimulated VSMC. But there was no difference in the protein expression of FAK among all the groups (P >0.05). Conclusion. IL- 10 antagonizes the VSMC proliferation and collagen synthesis by regulating FAK activity stimulated by AngII.展开更多
AIM:To investigate the effect of Clostridium difficile(C.difficile)infection in an interleukin 10-deficient(IL-10-/-)mouse model of inflammatory bowel disease.METHODS:Bone marrow-derived dendritic cells isolated from ...AIM:To investigate the effect of Clostridium difficile(C.difficile)infection in an interleukin 10-deficient(IL-10-/-)mouse model of inflammatory bowel disease.METHODS:Bone marrow-derived dendritic cells isolated from wild type(WT)and IL-10-/-mice were stimulated for 4 h with C.difficile toxin A(200μg/m L),and gene expression of interferon(IFN)-γ,IL-12 and IL-23was determined by real-time reverse transcription polymerase chain reaction.WT and IL-10-/-mice(n=20each)were exposed to an antibiotic cocktail for three days and then were injected with clindamycin(i.p.).Mice(n=10 WT,10 IL-10-/-)were then challenged with oral administration of C.difficile(1×105 colony forming units of strain VPI 10463).Animals were monitored daily for 7 d for signs of colitis.Colonic tissue samples were evaluated for cytokine gene expression and histopathologic analysis.RESULTS:C.difficile toxin A treatment induced IFN-γgene expression to a level that was significantly higher in BDMCs from IL-10-/-compared to those from WT mice(P<0.05).However,expression of IL-12 and IL-23 was not different among the groups.Following C.difficile administration,mice developed diarrhea and lost weight within 2-3 d.Weight loss was significantly greater in IL-10-/-compared to WT mice(P<0.05).C.difficile infection induced histopathologic features typical of colitis in both IL-10-/-and WT mice.The histopathologic severity score was significantly higher in the IL-10-/-than in WT mice(mean±standard error;5.50±0.53 vs 2.44±0.46;P<0.05).This was accompanied by a significantly greater increase in IFN-γgene expression in colonic tissues from IL-10-/-than from WT mice challenged with C.difficile(P<0.05).CONCLUSION:These results indicate that colitis is more severe after C.difficile infection in IL-10-/-mice,and that IFN-γexpression is involved in this process.展开更多
Trypanosomosis is major drawback to profitable livestock production in sub-Sahara African, including Nigeria. Knowledge of the cytokines production in the phase of natural infection may help to better diagnose, treat ...Trypanosomosis is major drawback to profitable livestock production in sub-Sahara African, including Nigeria. Knowledge of the cytokines production in the phase of natural infection may help to better diagnose, treat and prevent bovine trypanosomosis. The purpose of the this study was to determine the levels of interferon-gamma (IFN-γ), interleukin-10 (IL-10) and cardiac troponin–I (cTnI) in the sera of cattle naturally infected with T. brucei, T. congolense and T. vivax and correlate these levels with parasitaemia and PCV of the infected animals. Five milliliter of blood samples were collected via the jugular vein from 411 randomly selected cattle into EDTA and non-citrated bottle. PCV was determined manually using HCT. Trypansomes were detected and characterized by microscopy and PCR, respectively. Serum levels of IFN-γ, IL-10 and cTnI were determined using commercial ELISA kit. Data were summarized using descriptive statistic and significance of differences determined by ANOVA. Of the 62 samples positive for trypanosomes by microscopy, 50 samples were confirmed to species level by PCR. The sera levels of IFN-γ, IL-10 and cTnI of infected cattle were higher than non-infected cattle. The differences were not significant (p γ, IL-10 and cTnI in cattle with natural trypanosomosis. Further investigation is required to understand the specific effect of trypanosomes on myocardiac integrity and interaction between the two cytokines in natural trypanosomosis in cattle.展开更多
目的探讨脑脊液白细胞介素10(interleukin 10,IL-10)在原发性中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)中的诊断价值。方法收集作者医院2019-3-1—2022-12-31就诊并确诊的15例PCNSL患者、35例中枢神经系统脱...目的探讨脑脊液白细胞介素10(interleukin 10,IL-10)在原发性中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)中的诊断价值。方法收集作者医院2019-3-1—2022-12-31就诊并确诊的15例PCNSL患者、35例中枢神经系统脱髓鞘疾病(inflammatory demyelinating diseases of the CNS,IDDs)患者和6例原发性中枢神经系统血管炎(primary central nervous system vasculitis,PCNSV)患者的临床资料,采用自动电化学发光免疫法检测各组患者血清和脑脊液白细胞介素6(IL-6)和IL-10水平,采用多组秩和检验分析组间血清和脑脊液IL-6、IL-10水平的差异,采用Spearman相关分析PCNSL患者脑脊液IL-10与患者性别、病变部位、年龄、病灶数目、病程、病灶的最大径、病灶的最大标准摄取值(SUVmax)之间的关系。结果与IDDs组和PCNSV组比较,PCNSL患者脑脊液IL-10水平升高(P<0.01);ROC分析结果显示,脑脊液IL-10鉴别诊断PCNSL的曲线下面积为1,以11.45 pg/mL为临界值,其诊断的敏感性和特异性均为100%;Spearman相关性分析结果显示,PCNSL患者脑脊液IL-10与患者性别、年龄、病灶数目、病程、病灶的最大径、SUVmax均无相关性(P>0.05)。结论针对无法取得脑活检且疑诊PCNSL的患者于治疗前进行IL-10检测具有重要意义,脑脊液IL-10升高强烈提示PCNSL的诊断。展开更多
基金the National Natural Science Foundation of China,No.81741103.
文摘BACKGROUND Interleukin 10 receptor alpha subunit(IL10RA)dysfunction is the main cause of very early-onset inflammatory bowel disease(VEO-IBD)in East Asians.AIM To identify disease-causing gene mutations in four patients with VEO-IBD and verify functional changes related to the disease-causing mutations.METHODS From May 2016 to September 2020,four young patients with clinically diagnosed VEO-IBD were recruited.Before hospitalization,using targeted gene panel sequencing and trio-whole-exome sequencing(WES),three patients were found to harbor a IL10RA mutation(c.301C>T,p.R101W in one patient;c.537G>A,p.T179T in two patients),but WES results of the fourth patient were not conclusive.We performed whole-genome sequencing(WGS)on patients A and B and reanalyzed the data from patients C and D.Peripheral blood mononuclear cells(PBMCs)from patient D were isolated and stimulated with lipopolysaccharide(LPS),interleukin 10(IL-10),and LPS+IL-10.Serum IL-10 levels in four patients and tumor necrosis factor-α(TNF-α)in the cell supernatant were determined by enzyme-linked immunosorbent assay.Phosphorylation of signal transducer and activator of transcription 3(STAT3)at Tyr705 and Ser727 in PBMCs was determined by western blot analysis.RESULTS The four children in our study consisted of two males and two females.The age at disease onset ranged from 18 d to 9 mo.After hospitalization,a novel 333-bp deletion encompassing exon 1 of IL10RA was found in patients A and B using WGS and was found in patients C and D after reanalysis of their WES data.Patient D was homozygous for the 333 bp deletion.All four patients had elevated serum IL-10 levels.In vitro,IL-10-stimulated PBMCs from patient D failed to induce STAT3 phosphorylation at Tyr705 and only minimally suppressed TNF-αproduction induced by LPS.Phosphorylation at Ser727 in PBMCs was not affected by LPS or LPS+IL-10 in both healthy subjects and in patient D.CONCLUSION WGS revealed a novel 333-bp deletion of IL10RA in four patients with VEO-IBD,whereas the WES results were inconclusive.
文摘OBJECTIVES: To evaluate the behavior of serum interleukin 10 (IL-10) in patients with acutepancreatitis and to explore the relationship between this cytokine and the severity of the disease.METHODS: In 45 patients with acute pancreatitis, the serum concentrations of IL-10 was determinedon days 1, 2, 3, 4, 5 after admission. Twelve healthy subjects were also studied as controls. Thesesubjects were tested using a commercial ELISA kit. The severity of pancreatitis was determined accordingto APACHE Ⅱ score and Balthazar CT criteria.RESULTS: Healthy subjects had no detectable serum levels of IL-10. In acute pancreatitis patients,the serum IL-10 levels were increased on the first day after the onset of the disease and then progressivelydecreased in the following days. On the first day after the onset of acute pancreatitis, the serum levelsof IL-10 in patients with mild acute pancreatitis were significantly higher than in those with severe acutepancreatitis. In the following days, however, no statistically significant difference was observed betweenthe two groups.CONCLUSIONS: Serum IL-10 concentration reflects the severity of acute pancreatitis. IL-10 is a usefulvariable for early prediction of the prognosis of acute pancreatitis. The low values of serum IL-10 inpatients with severe acute pancreatitis suggests that there may be altered down-regulation of immunesystem response. An enhanced release of IL-10 may be a method for early treatment of acute pancreatitis.
基金This research was supported by the National Natural Sciences Foundation (No.39730220).
文摘Objective. To study the effect of interleukin 10 (IL- 10) on the angiotensin II (AngII) stimulated rat VSMC proliferation and collagen secretion, and furthermore, explore its mechanism. Methods. On cultured VSMC of rat, 3H- thymine (3H- TdR) and 3H- proline incorporations were used to evaluate the DNA and collagen synthesis, respectively. Western blot and immunoprecipitation were applied to assay the expression and activity of focal adhesion kinase (FAK), respectively. Results. IL- 10 (10－ 8～ 10－ 10g/ml) inhibited the increase of 3H- TdR and 3H- proline incorporation as well as FAK activity, which was induced by 10－ 7mol/L AngII (P< 0.05 or P< 0.01). IL- 10 also obviously downregulated the synthesis and secretion of collagen by AngII stimulated VSMC. But there was no difference in the protein expression of FAK among all the groups (P >0.05). Conclusion. IL- 10 antagonizes the VSMC proliferation and collagen synthesis by regulating FAK activity stimulated by AngII.
文摘AIM:To investigate the effect of Clostridium difficile(C.difficile)infection in an interleukin 10-deficient(IL-10-/-)mouse model of inflammatory bowel disease.METHODS:Bone marrow-derived dendritic cells isolated from wild type(WT)and IL-10-/-mice were stimulated for 4 h with C.difficile toxin A(200μg/m L),and gene expression of interferon(IFN)-γ,IL-12 and IL-23was determined by real-time reverse transcription polymerase chain reaction.WT and IL-10-/-mice(n=20each)were exposed to an antibiotic cocktail for three days and then were injected with clindamycin(i.p.).Mice(n=10 WT,10 IL-10-/-)were then challenged with oral administration of C.difficile(1×105 colony forming units of strain VPI 10463).Animals were monitored daily for 7 d for signs of colitis.Colonic tissue samples were evaluated for cytokine gene expression and histopathologic analysis.RESULTS:C.difficile toxin A treatment induced IFN-γgene expression to a level that was significantly higher in BDMCs from IL-10-/-compared to those from WT mice(P<0.05).However,expression of IL-12 and IL-23 was not different among the groups.Following C.difficile administration,mice developed diarrhea and lost weight within 2-3 d.Weight loss was significantly greater in IL-10-/-compared to WT mice(P<0.05).C.difficile infection induced histopathologic features typical of colitis in both IL-10-/-and WT mice.The histopathologic severity score was significantly higher in the IL-10-/-than in WT mice(mean±standard error;5.50±0.53 vs 2.44±0.46;P<0.05).This was accompanied by a significantly greater increase in IFN-γgene expression in colonic tissues from IL-10-/-than from WT mice challenged with C.difficile(P<0.05).CONCLUSION:These results indicate that colitis is more severe after C.difficile infection in IL-10-/-mice,and that IFN-γexpression is involved in this process.
文摘Trypanosomosis is major drawback to profitable livestock production in sub-Sahara African, including Nigeria. Knowledge of the cytokines production in the phase of natural infection may help to better diagnose, treat and prevent bovine trypanosomosis. The purpose of the this study was to determine the levels of interferon-gamma (IFN-γ), interleukin-10 (IL-10) and cardiac troponin–I (cTnI) in the sera of cattle naturally infected with T. brucei, T. congolense and T. vivax and correlate these levels with parasitaemia and PCV of the infected animals. Five milliliter of blood samples were collected via the jugular vein from 411 randomly selected cattle into EDTA and non-citrated bottle. PCV was determined manually using HCT. Trypansomes were detected and characterized by microscopy and PCR, respectively. Serum levels of IFN-γ, IL-10 and cTnI were determined using commercial ELISA kit. Data were summarized using descriptive statistic and significance of differences determined by ANOVA. Of the 62 samples positive for trypanosomes by microscopy, 50 samples were confirmed to species level by PCR. The sera levels of IFN-γ, IL-10 and cTnI of infected cattle were higher than non-infected cattle. The differences were not significant (p γ, IL-10 and cTnI in cattle with natural trypanosomosis. Further investigation is required to understand the specific effect of trypanosomes on myocardiac integrity and interaction between the two cytokines in natural trypanosomosis in cattle.
文摘目的探讨脑脊液白细胞介素10(interleukin 10,IL-10)在原发性中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)中的诊断价值。方法收集作者医院2019-3-1—2022-12-31就诊并确诊的15例PCNSL患者、35例中枢神经系统脱髓鞘疾病(inflammatory demyelinating diseases of the CNS,IDDs)患者和6例原发性中枢神经系统血管炎(primary central nervous system vasculitis,PCNSV)患者的临床资料,采用自动电化学发光免疫法检测各组患者血清和脑脊液白细胞介素6(IL-6)和IL-10水平,采用多组秩和检验分析组间血清和脑脊液IL-6、IL-10水平的差异,采用Spearman相关分析PCNSL患者脑脊液IL-10与患者性别、病变部位、年龄、病灶数目、病程、病灶的最大径、病灶的最大标准摄取值(SUVmax)之间的关系。结果与IDDs组和PCNSV组比较,PCNSL患者脑脊液IL-10水平升高(P<0.01);ROC分析结果显示,脑脊液IL-10鉴别诊断PCNSL的曲线下面积为1,以11.45 pg/mL为临界值,其诊断的敏感性和特异性均为100%;Spearman相关性分析结果显示,PCNSL患者脑脊液IL-10与患者性别、年龄、病灶数目、病程、病灶的最大径、SUVmax均无相关性(P>0.05)。结论针对无法取得脑活检且疑诊PCNSL的患者于治疗前进行IL-10检测具有重要意义,脑脊液IL-10升高强烈提示PCNSL的诊断。
