CpG-ODN调节Th1/Th2型细胞因子表达抑制放射性肺纤维化

CpG-ODN prevent pulmonary fibrosis by regulating the expression of Th1/Th2 cytokines

从Th细胞因子平衡的角度着手,探讨CpG-ODN在防治放射性肺纤维化中的作用机理。使用单次全肺照射15 Gy的雌性C57BL/6小鼠建立放射性肺损伤模型,通过酶联免疫吸附测定法连续20周检测小鼠体内Th1/Th2相关细胞因子和促纤维化细胞因子的表达水平,免疫组化法评估肺泡巨噬细胞、肺组织纤维化和丝裂原活化蛋白激酶(Mitogen-activated protein kinase,MAPK)家族主要蛋白的磷酸化水平。实验结果显示,CpG-ODN能促进Th1型细胞因子分泌,同时抑制Th2型细胞因子分泌,导致Th1型免疫反应占主导优势,从而抑制肺泡巨噬细胞的聚集活化,降低促纤维化细胞因子TGF-β1、IGF-1的表达,下调MAPK通路的活化。这提示CpG-ODN能通过调节电离辐射后Th1/Th2型细胞因子的失衡而抑制放射性肺纤维化的发生。

To investigate the mechanism of CpG-ODN in the prevention of radiation pulmonary fibrosis by focusing on the regulation of balance between Th1/Th2 cytokines. The entire thorax of female C57 BL/6 mice was exposed to a single radiation at a dose of 15 Gy. The Th1/Th2-related cytokines and profibrogenic cytokines were detected by enzyme linked immunosorbent assay for 20 weeks after radiation. Alveolar macrophages, pulmonary fibrosis, and phosphorylated Mitogen-activated protein kinase(MAPK) family proteins were detected by immunohistochemistry. The results suggested that CpG-ODN promoted Th1-related cytokine secretion and inhibited Th2-related cytokine secretion, leading to a predominantly Th1 immune response, reduced alveolar macrophage accumulation, and profibrogenic cytokine(TGF-β1 and IGF-1) expression, which may be involved in the inhibition of phosphorylation of MAPK family proteins. This indicates that CpG-ODN prevents pulmonary fibrosis by regulating the imbalance between Th1/Th2 after irradiation.