Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei, PR China; The Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei, PR China.
Int Immunopharmacol. 2013 Nov;17(3):537-42. doi: 10.1016/j.intimp.2013.07.020. Epub 2013 Aug 20.
Silicosis is one of the most prevalent occupational lung diseases, but the pathogenic mechanisms of silicosis are largely unknown and an effective treatment is not yet available. In this study, we investigated the potential effects of relaxin (RLX) on fibrosis by an in vitro model involving silica-induced and macrophage-mediated pulmonary fibroblasts. Following pre-treatment with DQ12 quartz, the culture supernatant of human monocytic THP-1 cells was added to human fetal lung fibroblast MRC-5 cells with or without RLX. DQ12 significantly induced an increase of TGFB1 mRNA in THP-1 cells, coinciding with elevated TGF-β1 protein excretion in the supernatant, but RLX had no effect on DQ12-stimulated TGF-β1 secretion in THP-1 cells. Furthermore, RLX inhibited the proliferation of MRC-5 cells, and reduced the mRNA level and protein secretion of collagen type I, whereas it increased the mRNA level and protein activity of MMP-2 in MRC-5 cells treated with THP-1 cell culture supernatant. Our data suggest that RLX may inhibit TGF-β1-mediated fibrosis during the process of silicosis, providing evidence for the protective effect of RLX on silica-induced pulmonary fibrosis.
矽肺是最常见的职业性肺部疾病之一，但矽肺的发病机制在很大程度上尚不清楚，也没有有效的治疗方法。在这项研究中，我们通过体外模型研究了松弛素（RLX）对纤维化的潜在影响，该模型涉及二氧化硅诱导和巨噬细胞介导的肺成纤维细胞。用 DQ12 石英对人单核细胞 THP-1 细胞进行预处理后，将人单核细胞 THP-1 细胞的培养上清液添加到人胎肺成纤维细胞 MRC-5 细胞中，同时添加或不添加 RLX。DQ12 显著诱导 THP-1 细胞中 TGFB1 mRNA 的增加，与上清液中 TGF-β1 蛋白排泄的升高一致，但 RLX 对 DQ12 刺激的 THP-1 细胞中 TGF-β1 分泌没有影响。此外，RLX 抑制 MRC-5 细胞的增殖，并降低 I 型胶原的 mRNA 水平和蛋白分泌，而在 THP-1 细胞培养上清液处理的 MRC-5 细胞中，它增加了 MMP-2 的 mRNA 水平和蛋白活性。我们的数据表明，RLX 可能在矽肺过程中抑制 TGF-β1 介导的纤维化，为 RLX 对二氧化硅诱导的肺纤维化的保护作用提供了证据。
