M2型巨噬细胞促分泌的IL-6因子对成纤维细胞活化的作用机制研究

特发性肺纤维化(idiopathic pulmonary fibrosis, IPF)通常伴有炎症反应,其中巨噬细胞与其密切相关,通过巨噬细胞与肺成纤维细胞共培养模型和博来霉素诱导的IPF小鼠模型,本文探究了巨噬细胞和白细胞介素-6(interleukin 6, IL-6)与IPF的联系。动物福利和实验过程均遵循天津中医药大学动物伦理委员会的规定。结果表明,博来霉素(bleomycin, BLM)诱导的IPF小鼠体内IL-6含量明显升高,且肺部有大量的炎性细胞浸润。划痕及免疫荧光实验结果表明,共培养36 h替代活化型(alternatively activated, M2)巨噬细胞可诱导成纤维细胞迁移及活化,且在共培养体系中IL-6的表达随之增多。划痕及天狼星红实验结果证明IL-6可促进成纤维细胞迁移和活化。研究结果证明, M2型巨噬细胞通过促进成纤维细胞分泌IL-6,从而诱导成纤维细胞活化及迁移,影响IPF发展。

Effect and mechanism of IL-6 induced by M2 macrophages on the lung fibroblasts activation

Idiopathic pulmonary fibrosis(IPF) is usually accompanied with inflammatory response, especially the macrophages. The co-culture model of macrophages and fibroblast, and IPF mice model induced by bleomycin were used here to explore the role of macrophages and interleukin-6(IL-6) in IPF. All animals welfare and experiments were performed following the regulations of the Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine. The results showed that the content of IL-6 in IPF mice induced by bleomycin was significantly increased, and there was a large amount of inflammatory cell infiltration in the lungs. The results of woundhealing and immunofluorescence showed that alternative activated(M2) macrophages could induce the migration and activation of fibroblasts at 36 h, and the expression of IL-6 was increased in the co-culture system. The results of wound-healing and sirius red assay proved that IL-6 could induce the migration and activation of fibroblast. The results showed that M2 macrophages induced fibroblasts to secrete IL-6, thereby inducing the activation and migration of fibroblast, which affect the development of IPF.