IL-17、IL-22和IL-10在支气管哮喘患儿外周血单个核细胞中的表达及意义
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摘要
目的探讨白细胞介素(IL)-17、IL-22和IL-10在支气管哮喘患儿外周血单个核细胞中的表达及意义。方法选取75例哮喘患儿,根据病情分为发作组(41例)和缓解组(34例),以体检健康儿童40名作为正常对照组。分离所有对象的外周血单个核细胞,分别采用实时定量聚合酶链反应(PCR)及免疫印迹法检测外周血单个核细胞中IL-17、IL-22和IL-10基因及蛋白的表达,同时检测所有对象的肺功能[第1秒用力呼气量(FEV1)、FEV1/用力肺活量(FVC)比值]。采用Pearson相关分析评估各项目间的相关性。结果发作组FEV1和FEV1/FVC比值均低于缓解组和正常对照组(P<0.05),且缓解组低于正常对照组(P<0.05)。发作组外周血单个核细胞中IL-17、IL-22 mRNA和蛋白的相对表达量均高于缓解组和正常对照组(P<0.05),且缓解组高于正常对照组(P<0.05);而IL-10 mRNA和蛋白的相对表达量均低于缓解组和正常对照组(P<0.05),且缓解组低于正常对照组(P<0.05)。哮喘患儿外周血单个核细胞中IL-17、IL-22 mRNA和蛋白的相对表达量与IL-10 mRNA和蛋白的相对表达量、FEV1、FEV1/FVC比值均呈负相关(P<0.05),IL-10 mRNA和蛋白的相对表达量与FEV1、FEV1/FVC比值均呈正相关(P<0.05)。结论哮喘患儿外周血单个核细胞中IL-17、IL-22表达上调,而IL-10表达下调,且与患儿病情有关,提示辅助性T细胞17(Th17)/调节性T细胞(Treg)比例失调可能参与了哮喘发病。
Objective To investigate the expressions of interleukin(IL)-17,IL-22 and IL-10 in peripheral blood mononuclear cells in children with bronchial asthma. Methods A total of 75 children with asthma were classified into exacerbation group(41 cases) and remission group(34 cases). A total of 40 healthy children were enrolled as control group. The peripheral blood mononuclear cells were isolated. The expressions of IL-17,IL-22 and IL-10 genes in peripheral blood mononuclear cells were determined by real-time quantitation polymerase chain reaction(PCR). The expressions of IL-17,IL-22 and IL-10 proteins in peripheral blood mononuclear cells were determined by western blotting. The forced expiratory volume in 1 second(FEV1) and the ratio of FEV1/forced vital capacity(FVC) were determined. The correlations among the variables were analyzed by Pearson correlation analysis. Results The FEV1 and FEV1/FVC in exacerbation group were lower than those in remission group and control group(P<0.05),and those in remission group were lower than those in control group(P<0.05). The relative expression levels of IL-17 mRNA and IL-22 mRNA in peripheral blood mononuclear cells in exacerbation group were higher than those in remission group and control group(P<0.05),and those in remission group were higher than those in control group(P<0.05). However, the relative expression level of IL-10 mRNA was lower than those in remission group and control group(P<0.05),and that in remission group was lower than that in control group(P<0.05). The relative expression levels of IL-17 mRNA, IL-17 protein and IL-22 mRNA, IL-22 protein in peripheral blood mononuclear cells in asthmatic children were negatively correlated with the relative expression levels of IL-10 mRNA and IL-10 protein,FEV1 and FEV1/FVC(P<0.05),and the relative expression levels of IL-10 mRNA and IL-10 protein were positively correlated with FEV1 and FEV1/FVC(P<0.05). Conclusions The expressions of IL-17 and IL-22 in peripheral blood mononuclear cells of children with asthma are upregulated,while the expression of IL-10 is downregulated,which are related with disease status. It prompts that T helper cell 17(Th17)/regulatory T cell(Treg) imbalance might be involved in the pathogenesis of asthma.
Objective To investigate the expressions of interleukin(IL)-17,IL-22 and IL-10 in peripheral blood mononuclear cells in children with bronchial asthma. Methods A total of 75 children with asthma were classified into exacerbation group(41 cases) and remission group(34 cases). A total of 40 healthy children were enrolled as control group. The peripheral blood mononuclear cells were isolated. The expressions of IL-17,IL-22 and IL-10 genes in peripheral blood mononuclear cells were determined by real-time quantitation polymerase chain reaction(PCR). The expressions of IL-17,IL-22 and IL-10 proteins in peripheral blood mononuclear cells were determined by western blotting. The forced expiratory volume in 1 second(FEV1) and the ratio of FEV1/forced vital capacity(FVC) were determined. The correlations among the variables were analyzed by Pearson correlation analysis. Results The FEV1 and FEV1/FVC in exacerbation group were lower than those in remission group and control group(P<0.05),and those in remission group were lower than those in control group(P<0.05). The relative expression levels of IL-17 mRNA and IL-22 mRNA in peripheral blood mononuclear cells in exacerbation group were higher than those in remission group and control group(P<0.05),and those in remission group were higher than those in control group(P<0.05). However, the relative expression level of IL-10 mRNA was lower than those in remission group and control group(P<0.05),and that in remission group was lower than that in control group(P<0.05). The relative expression levels of IL-17 mRNA, IL-17 protein and IL-22 mRNA, IL-22 protein in peripheral blood mononuclear cells in asthmatic children were negatively correlated with the relative expression levels of IL-10 mRNA and IL-10 protein,FEV1 and FEV1/FVC(P<0.05),and the relative expression levels of IL-10 mRNA and IL-10 protein were positively correlated with FEV1 and FEV1/FVC(P<0.05). Conclusions The expressions of IL-17 and IL-22 in peripheral blood mononuclear cells of children with asthma are upregulated,while the expression of IL-10 is downregulated,which are related with disease status. It prompts that T helper cell 17(Th17)/regulatory T cell(Treg) imbalance might be involved in the pathogenesis of asthma.
引文
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[9]SHI Y H,SHI G C,WAN H Y,et al.Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with allergic asthma[J].Chin Med J(Engl),2011,124(13):1951-1956.
[10]NARBUTT J,WOJTCZAK M,ZALINˊSKA A,et al.The A/A genotype of an interleukin-17A polymorphism predisposes to increased severity of atopic dermatitis and coexistence with asthma[J].Clin Exp Dermatol,2015,40(1):11-16.
[11]MANNI M L,ROBINSON K M,ALCORN J F.A tale of two cytokines:IL-17 and IL-22 in asthma and infection[J].Expert Rev Respir Med,2014,8(1):25-42.
[12]B?HM L,MAXEINER J,MEYER-MARTIN H,et al.IL-10 and regulatory T cells cooperate in allergenspecific immunotherapy to ameliorate allergic asthma[J].JImmunol,2015,194(3):887-897.
[2]沙莉,刘传合,邵明军,等.中国城市儿童哮喘诊治状况十年对比[J].中华儿科杂志,2016,54(3):182-186.
[3]王艳丽,陆小霞,陈鹏,等.Tim-3在哮喘小鼠中的表达及与Th17/Treg细胞的关系[J].实用医学杂志,2015,31(7):1095-1098.
[4]CHEN F,CAO A,YAO S,et al.mTOR mediates IL-23 induction of neutrophil IL-17 and IL-22 production[J].JImmunol,2016,196(10):4390-4399.
[5]AZIZI G,YAZDANI R,MIRSHAFIEY A.Th22 cells in autoimmunity:a review of current knowledge[J].Eur Ann Allergy Clin Immunol,2015,47(4):108-117.
[6]ZHU X M,HUANG Y M,FAN J F,et al.Aberrant frequency of IL-10-producing B cells and its association with the balance of Treg/Th17 in children with inflammatory bowel disease[J].Pharmazie,2015,70(10):656-660.
[7]KOCH S,REPPERT S,FINOTTO S.NFATc1 deletion in T lymphocytes inhibits the allergic trait in a murine model of asthma[J].Clin Exp Allergy,2015,45(8):1356-1366.
[8]HOU X,WAN H,AI X,et al.Histone deacetylase inhibitor regulates the balance of Th17/Treg in allergic asthma[J].Clin Respir J,2016,10(3):371-379.
[9]SHI Y H,SHI G C,WAN H Y,et al.Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with allergic asthma[J].Chin Med J(Engl),2011,124(13):1951-1956.
[10]NARBUTT J,WOJTCZAK M,ZALINˊSKA A,et al.The A/A genotype of an interleukin-17A polymorphism predisposes to increased severity of atopic dermatitis and coexistence with asthma[J].Clin Exp Dermatol,2015,40(1):11-16.
[11]MANNI M L,ROBINSON K M,ALCORN J F.A tale of two cytokines:IL-17 and IL-22 in asthma and infection[J].Expert Rev Respir Med,2014,8(1):25-42.
[12]B?HM L,MAXEINER J,MEYER-MARTIN H,et al.IL-10 and regulatory T cells cooperate in allergenspecific immunotherapy to ameliorate allergic asthma[J].JImmunol,2015,194(3):887-897.