白细胞介素-33在外周血中表达变化及调控肺上皮细胞在肺炎支原体肺炎患儿发病中的作用

Changes of interleukin-33 expression in peripheral blood and its role in regulating pulmonary epithelial cells in children with Mycoplasma pneumoniae pneumonia

目的探讨肺炎支原体肺炎(MPP)患儿体内白细胞介素(IL)-33表达水平与其在疾病发展中的作用。方法将60例MPP患儿按照病情严重程度分为MPP组30例及重症MPP组30例,同期选取年龄相近的健康儿童30例作为对照组。利用荧光定量PCR技术及酶联免疫技术检测IL-33在患儿及对照儿童外周血及外周血单核细胞中的表达差异,利用荧光定量PCR技术检测IL-33上游炎性小体信号通路变化,利用体外表达的IL-33刺激肺上皮细胞研究IL-33在炎症发生发展过程中的作用。结果 MPP组及重症MPP组患儿外周血中IL-33蛋白表达水平及外周血单核细胞中IL-33 mRNA的表达水平远高于对照组儿童,且重症组患儿表达量更高,差异均有统计学意义(P<0.05)。MPP组及重症MPP组患儿外周血单核细胞中炎性小体信号通路活性显著上调且NLRP3等相关基因表达量远高于对照组儿童,差异有统计学意义(P<0.01)。MPP组及重症MPP组患儿NLRP3表达量与IL-33表达量具有正相关关系(r2=0.685 2,P<0.01)。体外表达的IL-33能够明显诱导支气管上皮细胞产生及分泌IL-6等炎症因子,并促进炎症的发生发展。结论 IL-33在MPP患儿中表达量显著高于正常人群,且IL-33的表达量可以作为判别MPP病症严重与否的检测标志物。IL-33产生于单核细胞炎性小体信号通路激活,进一步促进肺上皮细胞产生炎症因子并促进炎症的发生发展。

Objective To explore the expression level of interleukin-33( IL-33) in children with Mycoplasma pneumoniae pneumonia( MPP) and its role in occurrence and development of MPP. Methods Sixty MPP children were divided into severe MPP group and mild MPP group according to severity of the disease,30 children in each group,30 age-matched healthy children were selected as control group during the same period. Fluorescent quantitative PCR and ELISA were used to detect the differences of IL-33 expressions in peripheral blood and peripheral blood mononuclear cells in the three groups. Fluorescent quantitative PCR was used to detect the changes of IL-33 upstream inflammasome signal pathway. IL-33 expressed in vitro was used to stimulate pulmonary epithelial cells to research the role of IL-33 in occurrence and development of inflammation. Results The expression levels of IL-33 protein in peripheral blood and IL-33 mRNA in peripheral blood mononuclear cells in mild MPP group and severe MPP group were statistically significantly higher than those in control group,the expression levels of IL-33 protein in peripheral blood and IL-33 mRNA in peripheral blood mononuclear cells in severe MPP group were statistically significantly higher than those in mild MPP group( P< 0. 05). The activity of inflammasome signal pathway in peripheral blood mononuclear cells in mild MPP group and severe MPP group increased significantly,the expression level of NLRP3 in mild MPP group and severe MPP group were statistically significantly higher than that in control group( P<0. 01). In mild MPP group and severe MPP group,NLRP3 expression level was positively correlated with IL-33 expression level( r2= 0. 6852,P<0. 01). IL-33 expressed in vitro could induce secretion of inflammatory cytokines in bronchial epithelial cells,such as IL-6,which also can promote occurrence and development of inflammation. Conclusion The expression level of IL-33 in MPP children is significantly higher than that in normal children,which can be used to estimate the severity of MPP,IL-33 is produced by activation of inflammasome signal pathway in peripheral blood mononuclear cells,which can further promote secretion of inflammatory cytokines in bronchial epithelial cells,occurrence and development of inflammation.