TGF-β_1对人胚肺成纤维细胞基质金属蛋白酶及其组织抑制因子表达的影响  

Effect of TGF-β_1 on the Expression of MMP-1 and TIMP-1 in Human Lung Fibroblasts in vitro

作　　者：马小兵[1] 李秀玲[2] 孙树勋[1] 杨方[1] 

机构地区：[1]华北煤炭医学院,河北唐山063000 [2]开滦医疗集团林西医院,河北唐山063103

出　　处：《工业卫生与职业病》2006年第2期71-74,共4页Industrial Health and Occupational Diseases

摘　　要：目的探讨SiO2是否通过转化生长因子β(TGFβ-1)影响肺成纤维细胞(FB)中基质金属蛋白酶(MMPs)/金属蛋白酶组织抑制因子(TIMPs)的表达而参与矽肺纤维化的发生发展。方法收集矽肺病人肺泡巨噬细胞(AM)培养上清,与人胚肺成纤维细胞(FB)共同孵育6 h和24 h,并用TGF-β1抗体进行干预,用免疫细胞化学的方法检测FB中MMP-1和TIMP-1的表达。结果经SiO2刺激的矽肺病人AM培养上清作用于FB,与对照组比较,可使FB中MMP-1的表达减少(吸光度A值0.062±0.008 vs 0.103±0.014,24 h),可使TIMP-1的表达增多(吸光度A值0.143±0.015 vs 0.108±0.012,24 h);加入TGF-β1抗体可逆转此作用。结论TGF-β1可影响AM介导的FB中MMP-1/TIMP-1系统的表达。Objective To study the effect and mechanism of SiO2 on the expression of matrix metalloproteinases-1 （MMP-1） and tissue inhibitor of metalloproteinases-1 （TIMP-1） in human lung fibroblasts. Methods Human alveolar macrophages were collected from a silieotic by BAL and exposed to SiO2 for 18 h, and then the conditioned supernatants were collected. The human fetal lung fibroblasts were isolated by tyrosine dispersion method, and incubated with the conditioned supernatant on human alveolar macrophages and anti-TGF-β1 antibody for 6 h and 24 h. Immunocytochemical method was used to detect the level in the expression of MMP-1 and TIMP-1 in lung fibroblasts. Results The effect of the supernatant of alveolar macrophages exposed to SiO2 for 18 h that decrease the product MMP-1 but stimulate the expression of TIMP-1 in lung fibroblasts could be reversed by anti-TGF-β1 antibody. Conclusions The imbalance between MMPs and TIMPs in lung fibroblasts mediated by cytokines such as TGF-β1 contributed to the pathogenesis of silicosis.

关 键 词：TGF-Β 肺泡巨噬细胞 肺成纤维细胞 基质金属蛋白酶-1 金属蛋白酶组织抑制因子-1 

分 类 号：R114[医药卫生—卫生毒理学]