目的观察胱天蛋白酶募集域蛋白9(CARD9)在急性中重度缺血性脑卒中发病早期阶段的作用,探讨脑卒中炎症的发病机制。方法入选36例美国国立卫生研究院卒中量表(NIHSS)评分> 5分的急性中度及以上缺血性脑卒中患者为病例组;入选20例年龄...目的观察胱天蛋白酶募集域蛋白9(CARD9)在急性中重度缺血性脑卒中发病早期阶段的作用,探讨脑卒中炎症的发病机制。方法入选36例美国国立卫生研究院卒中量表(NIHSS)评分> 5分的急性中度及以上缺血性脑卒中患者为病例组;入选20例年龄、高血压、糖尿病等基础病与病例组差异无统计学意义的志愿者作为对照组。采集病例组发病第1、3、7天及对照组第1天外周血单个核细胞(PBMC)。Western blot检测CARD9表达水平及核转录因子-κB(NF-κB)活性(p-p65/p65水平);RT-PCR检测炎症因子肿瘤坏死因子-ɑ(TNF-ɑ)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6) mRNA的表达水平;病例组第1、3、7天使用NIHSS评分评估脑缺血损伤程度。结果 Western blot结果表明,入院第1、3、7天时,病例组CARD9表达及NF-κB活性与对照组比较显著升高(CARD9:1.17±0.14、1.08±0.15、0.97±0.16 vs. 0.34±0.02,NF-κB:1.78±0.06、1.70±0.07、1.46±0.04 vs. 1.21±0.12,P均<0.05);RT-PCR结果表明,入院第1、3、7天时,病例组TNF-αmRNA表达与对照组比较显著升高(5.34±0.14、4.57±0.15、3.58±0.19 vs. 1.00±0.08,P均<0.01),病例组IL-1βmRNA表达与对照组比较显著升高(6.49±0.12、4.85±0.23、3.38±0.31 vs. 1.00±0.11,P均<0.01),病例组IL-6 mRNA表达与对照组比较显著升高(10.29±0.55、7.32±0.44、4.56±0.33 vs. 1.00±0.07,P均<0.01)。Pearson相关分析表明,脑卒中患者PBMC中NF-κB活化、TNF-α、IL-1β、IL-6 mRNA及NIHSS评分与CARD9表达呈正相关(r值分别为0.971、0.974、0.970、0.982、0.891,P均<0.01)。结论 CARD9在早期中重度缺血性脑卒中患者PBMC中的表达增高,可能通过NF-κB信号通路介导缺血性脑损伤炎症反应。展开更多
Caspase recruitment domain containing protein 9(CARD9)is an adaptor protein that plays a critical role in pattern recognition receptors(PRRs)-mediated activation of NF-kB and mitogen-activated protein kinase(MAPK).Thi...Caspase recruitment domain containing protein 9(CARD9)is an adaptor protein that plays a critical role in pattern recognition receptors(PRRs)-mediated activation of NF-kB and mitogen-activated protein kinase(MAPK).This elicits initiation of the pro・inflammatory cytokines and leads to inflammatory responses,which has been recognized as a critical contributor to chronic inflammation.Current researches demonstrate that CARD9 is strongly associated with metabolic diseases,such as obesity,insulin resistance,atherosclerosis and so on.In this review,we summarize CARD9 signaling pathway and the role of CARD9 in metabolic diseases.展开更多
AIM:To investigate the interaction of interleukin-23 receptor(IL23R)(rs1004819 and rs2201841),autophagy-related 16-like 1(ATG16L1)(rs2241880), caspase recruitment domain-containing protein 15 (CARD15)genes,and IBD5 lo...AIM:To investigate the interaction of interleukin-23 receptor(IL23R)(rs1004819 and rs2201841),autophagy-related 16-like 1(ATG16L1)(rs2241880), caspase recruitment domain-containing protein 15 (CARD15)genes,and IBD5 locus in Crohn's disease(CD) patients. METHODS:A total of 315 unrelated subjects with CD and 314 healthy controls were genotyped.Interactions and specific genotype combinations of a total of eight variants were tested.The variants of IBD5locus(IGR2198a_1 rs11739135 and IGR2096a_1 rs12521868),CARD15(R702W rs2066845 and L1007fs rs2066847),ATG16L1(rs2241880)and IL23R (rs1004819,rs2201841)genes were genotyped by PCR-RFLP,the G908R(rs2066844)in CARD15 was determined by direct sequencing. RESULTS:The association of ATG16L1 T300A with CD was confirmed[P=0.004,odds ratio(OR)=1.69, 95%CI:1.19-2.41],and both IL23R variants were found to represent significant risk for the disease(P= 0.008,OR=2.05,95%CI:1.20-3.50 for rs1004819 AA;P<0.001,OR=2.97,95%CI:1.65-5.33 for rs2201841 CC).Logistic regression analysis of pairwise interaction of the inflammatory bowel disease (IBD)loci indicated that IL23R,ATG16L1,CARD15 and IBD5(IGR2198a_1)contribute independently to disease risk.We also analysed the specific combina- tions by pair of individual ATG16L1,IL23R rs1004819, rs2201841,IGR2198a_1,IGR2096a_1 and CARD15 genotypes for disease risk influence.In almost all cases,the combined risk of susceptibility pairs was higher in patients carrying two different risk-associated gene variants together than individuals with just one polymorphism.The highest OR was found for IL23R rs2201841 homozygous genotype with combination of positive CARD15 status(P<0.001,OR=9.15,95% CI:2.05-40.74). CONCLUSION:The present study suggests a cumulative effect of individual IBD susceptibility loci.展开更多
文摘目的观察胱天蛋白酶募集域蛋白9(CARD9)在急性中重度缺血性脑卒中发病早期阶段的作用,探讨脑卒中炎症的发病机制。方法入选36例美国国立卫生研究院卒中量表(NIHSS)评分> 5分的急性中度及以上缺血性脑卒中患者为病例组;入选20例年龄、高血压、糖尿病等基础病与病例组差异无统计学意义的志愿者作为对照组。采集病例组发病第1、3、7天及对照组第1天外周血单个核细胞(PBMC)。Western blot检测CARD9表达水平及核转录因子-κB(NF-κB)活性(p-p65/p65水平);RT-PCR检测炎症因子肿瘤坏死因子-ɑ(TNF-ɑ)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6) mRNA的表达水平;病例组第1、3、7天使用NIHSS评分评估脑缺血损伤程度。结果 Western blot结果表明,入院第1、3、7天时,病例组CARD9表达及NF-κB活性与对照组比较显著升高(CARD9:1.17±0.14、1.08±0.15、0.97±0.16 vs. 0.34±0.02,NF-κB:1.78±0.06、1.70±0.07、1.46±0.04 vs. 1.21±0.12,P均<0.05);RT-PCR结果表明,入院第1、3、7天时,病例组TNF-αmRNA表达与对照组比较显著升高(5.34±0.14、4.57±0.15、3.58±0.19 vs. 1.00±0.08,P均<0.01),病例组IL-1βmRNA表达与对照组比较显著升高(6.49±0.12、4.85±0.23、3.38±0.31 vs. 1.00±0.11,P均<0.01),病例组IL-6 mRNA表达与对照组比较显著升高(10.29±0.55、7.32±0.44、4.56±0.33 vs. 1.00±0.07,P均<0.01)。Pearson相关分析表明,脑卒中患者PBMC中NF-κB活化、TNF-α、IL-1β、IL-6 mRNA及NIHSS评分与CARD9表达呈正相关(r值分别为0.971、0.974、0.970、0.982、0.891,P均<0.01)。结论 CARD9在早期中重度缺血性脑卒中患者PBMC中的表达增高,可能通过NF-κB信号通路介导缺血性脑损伤炎症反应。
基金This study was supported by the National Natural Science Foundation of China(No.81872000).
文摘Caspase recruitment domain containing protein 9(CARD9)is an adaptor protein that plays a critical role in pattern recognition receptors(PRRs)-mediated activation of NF-kB and mitogen-activated protein kinase(MAPK).This elicits initiation of the pro・inflammatory cytokines and leads to inflammatory responses,which has been recognized as a critical contributor to chronic inflammation.Current researches demonstrate that CARD9 is strongly associated with metabolic diseases,such as obesity,insulin resistance,atherosclerosis and so on.In this review,we summarize CARD9 signaling pathway and the role of CARD9 in metabolic diseases.
基金Supported by Grant of Hungarian Scientific Research Foundation,No.OTKA T 73430
文摘AIM:To investigate the interaction of interleukin-23 receptor(IL23R)(rs1004819 and rs2201841),autophagy-related 16-like 1(ATG16L1)(rs2241880), caspase recruitment domain-containing protein 15 (CARD15)genes,and IBD5 locus in Crohn's disease(CD) patients. METHODS:A total of 315 unrelated subjects with CD and 314 healthy controls were genotyped.Interactions and specific genotype combinations of a total of eight variants were tested.The variants of IBD5locus(IGR2198a_1 rs11739135 and IGR2096a_1 rs12521868),CARD15(R702W rs2066845 and L1007fs rs2066847),ATG16L1(rs2241880)and IL23R (rs1004819,rs2201841)genes were genotyped by PCR-RFLP,the G908R(rs2066844)in CARD15 was determined by direct sequencing. RESULTS:The association of ATG16L1 T300A with CD was confirmed[P=0.004,odds ratio(OR)=1.69, 95%CI:1.19-2.41],and both IL23R variants were found to represent significant risk for the disease(P= 0.008,OR=2.05,95%CI:1.20-3.50 for rs1004819 AA;P<0.001,OR=2.97,95%CI:1.65-5.33 for rs2201841 CC).Logistic regression analysis of pairwise interaction of the inflammatory bowel disease (IBD)loci indicated that IL23R,ATG16L1,CARD15 and IBD5(IGR2198a_1)contribute independently to disease risk.We also analysed the specific combina- tions by pair of individual ATG16L1,IL23R rs1004819, rs2201841,IGR2198a_1,IGR2096a_1 and CARD15 genotypes for disease risk influence.In almost all cases,the combined risk of susceptibility pairs was higher in patients carrying two different risk-associated gene variants together than individuals with just one polymorphism.The highest OR was found for IL23R rs2201841 homozygous genotype with combination of positive CARD15 status(P<0.001,OR=9.15,95% CI:2.05-40.74). CONCLUSION:The present study suggests a cumulative effect of individual IBD susceptibility loci.
