TIPE2对肺炎支原体感染的负向调控作用及其机制研究  

The negative role and its underlying mechanism of TIPE2 on mycoplasma pneumoniae infection

作　　者：陈建萍[1] 余荣环[2] 胡新华[3] CHEN Jian-ping;YU Rong-huan;HU Xin-hua(Shanghai University of Medicine&Health Sciences Health Care Center,Shanghai 200237,China;Department of Respiratory Medicine,Shanghai Xuhui District Central Hospital,Shanghai 200031,China;Department of ICU,Shanghai Xuhui District Central Hospital,Shanghai 200031,China)

机构地区：[1]上海健康医学院卫生保健中心,上海200237 [2]上海市徐汇区中心医院呼吸内科,上海200031 [3]上海市徐汇区中心医院重症医学科,上海200031

出　　处：《河北医科大学学报》2018年第3期252-257,共6页Journal of Hebei Medical University

摘　　要：目的探讨肿瘤坏死因子α诱导蛋白8家族样蛋白2(tumor necrosis factor-alpha-induced protein-8like-2protein,TIPE2)对肺炎支原体感染(mycoplasma pneumoniae pneumonia,MPP)的负向调控作用及其机制。方法选取MPP患儿142例,根据临床表现分为普通MPP组78例和难治性肺炎支原体肺炎(refractory mycoplasma pneumoniae pneumonia,RMPP)组64例。检测所有患儿外周血中TIPE2表达的变化,并与65例健康儿童外周血中TIPE2表达的变化进行对照。在细胞试验中检测感染肺炎支原体(mycoplasma pneumoniae,MP)后TIPE2的水平。通过干扰实验研究其对MPP的调控。通过Western-blot实验研究其调控机制。结果普通MPP组和RMPP组外周血单核细胞中TIPE2mRNA表达水平低于对照组,RMPP组低于普通MPP组(P<0.05)。随着MP浓度增加,THP-1细胞分化成的巨噬细胞TIPE2mRNA及其蛋白灰度值逐渐降低(P<0.05)。MP浓度与TIPE2mRNA及其蛋白表达呈负相关(P<0.05)。感染MP后巨噬细胞分泌IL-6、TNF-α、IL-1β的量明显升高,MP浓度为50CFU/cell浓度时,细胞因子IL-6、TNF-α、IL-1β分泌量最高(P<0.05)。以MP在50CFU/cell浓度刺激巨噬细胞,随时间增加,IL-6、TNF-α、IL-1β水平明显升高(P<0.05)。SiRNA组IL-6、TNF-α、IL-1β水平明显高于非SiRNA组(P<0.05)。结论感染MP后患儿TIPE2表达水平明显降低,并且与疾病严重程度呈负相关。体外实验表明MPP可抑制TIPE2的表达,而TIPE2可以对MAPK通路产生抑制作用,从而负调节炎症因子的水平。Objective To investigate the negative regulatory effect of tumor necrosis factor-alpha-induced protein-8 like-2 protein(TIPE2)on mycoplasma pneumoniae pneumonia(MPP)and its mechanism.Methods A total of 142 children with MPP were selected and divided into MPP group(78 cases)and refractory mycoplasma pneumoniae pneumonia(RMPP,64 cases)according to their clinical manifestations.The changes of TIPE2 expression in peripheral blood of all children were detected and compared with the changes of TIPE2 expression in peripheral blood of 65 healthy children.The level of TIPE2 after infection with mycoplasma pneumoniae(MP)was tested in a cell assay.Results The levels of TIPE2 mRNA in peripheral blood mononuclear cells in children with MPP and RMPP were lower than those in control group,and those in RMPP group were lower than those in normal MPP group(P<0.05).With the increase of MP concentration,TIPE2 mRNA and protein gray value of THP-1 cells differentiated into macrophages were gradually decreased(P<0.05).MP concentration and TIPE2 mRNA and protein expression were negatively correlated(P<0.05).The amount of IL-6,TNF-αand IL-1βsecreted by macrophages was significantly increased after infected with MP,and the highest secretion of IL-6,TNF-αand IL-1βwas found when the concentration of MP was 50 CFU/cell(P<0.05).The levels of IL-6,TNF-αand IL-1βwere significantly increased with the increasement of MP stimulation at 50 CFU/cell(P<0.05).The levels of IL-6,TNF-αand IL-1βin SiRNA group were significantly higher than those in non-SiRNA group(P<0.05).Conclusion The level of TIPE2 expression in children with MP infection was significantly lower and negatively correlated with the severity of the disease.In vitro experiments show that MPP can inhibit TIPE2 expression,and TIPE2 can inhibit the MAPK pathway,which negatively regulate the level of inflammatory cytokines.

关 键 词：肺炎支原体 TIPE2 炎症因子 

分 类 号：R375.2[医药卫生—病原生物学]