Liu Juan, Shang Biao, Bai Jing
Department of Pediatrics, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Exp Ther Med. 2020 Sep;20(3):2148-2156. doi: 10.3892/etm.2020.8931. Epub 2020 Jun 24.
Asthma in children poses a threat to their health, but the mechanism remains to be elucidated. The present study investigated the mechanism by which the interleukin (IL)-22/IL-22 receptor 1 (IL-22R1) signaling pathway regulates subepithelial fibrosis in children with asthma. A total of 41 children with asthma and 12 healthy children were included in the present study. ELISA was performed to measure the content of IL-22 in peripheral blood. Serum from children with asthma was used to incubate MRC-5 cells and IL-22 antibody rescued the effect of IL-22 on the biological functions of MRC-5 cells. Reverse transcription-quantitative PCR was performed to determine IL-22R1 mRNA expression levels and western blotting was performed to measure IL-22R1 protein expression. The Cell Counting Kit-8 assay was used to analyze cell proliferation and flow cytometry was performed to assess the cell cycle distribution of MRC-5 cells. The expression of IL-22 was elevated in peripheral blood from children with asthma, which promoted the proliferation of MRC-5 cells, possibly via the upregulation of collagen type I α1 chain (COL1α1) and collagen type I α2 chain (COL1α2). IL-22 exerted its biological functions via IL-22R1. The IL-22/IL-22R1 signaling pathway regulated the proliferation of MRC-5 cells and the expression of COL1α1 and COL1α2 in MRC-5 cells via the JAK/STAT3 signaling pathway. Mononuclear lymphocytes from children with asthma stimulated the proliferation and secretory function of fibroblasts by secreting IL-22. The present study suggested that IL-22 expression in peripheral blood of children with asthma is upregulated compared with the control group. Furthermore, the present study indicated that the IL-22/IL-22R1 signaling pathway promoted MRC-5 cell proliferation and collagen synthesis by activating the JAK/STAT3 signaling pathway, thereby potentially regulating airway subepithelial fibrosis.
儿童哮喘对其健康构成威胁，但其机制仍有待阐明。本研究探讨白细胞介素（IL）-22/IL-22受体1（IL-22R1）信号通路调节儿童哮喘患者上皮下纤维化的机制。本研究共纳入41例哮喘儿童和12例健康儿童。采用酶联免疫吸附测定（ELISA）法检测外周血中IL-22的含量。用哮喘儿童的血清培养人胚肺成纤维细胞（MRC-5细胞），IL-22抗体可逆转IL-22对MRC-5细胞生物学功能的影响。采用逆转录-定量聚合酶链反应（RT-qPCR）检测IL-22R1 mRNA表达水平，蛋白质免疫印迹法检测IL-22R1蛋白表达。采用细胞计数试剂盒-8（CCK-8）法分析细胞增殖情况，流式细胞术检测MRC-5细胞的细胞周期分布。哮喘儿童外周血中IL-22表达升高，可能通过上调Ⅰ型胶原α1链（COL1α1）和Ⅰ型胶原α2链（COL1α2）促进MRC-5细胞增殖。IL-22通过IL-22R1发挥其生物学功能。IL-22/IL-22R1信号通路通过Janus激酶/信号转导和转录激活因子3（JAK/STAT3）信号通路调节MRC-5细胞的增殖以及COL1α1和COL1α2在MRC-5细胞中的表达。哮喘儿童的单核淋巴细胞通过分泌IL-22刺激成纤维细胞的增殖和分泌功能。本研究提示，与对照组相比，哮喘儿童外周血中IL-22表达上调。此外，本研究表明，IL-22/IL-22R1信号通路通过激活JAK/STAT3信号通路促进MRC-5细胞增殖和胶原合成，从而可能调节气道上皮下纤维化。
