Mycobacterium tuberculosis Effects on Fibroblast Collagen Metabolism

Background: Type I collagen synthesis and degradation are important events during Mycobacterium tuberculosis (MTb) granuloma or cavity formation, and fibroblasts are cells involved in these processes. Objective: We examined the MTb effects on fibroblast collagen metabolism to understand the virulence factors involved in tuberculosis pathogenesis. Methods: Human lung fibroblasts were incubated with culture medium or sonicated MTb H37Ra (avirulent) or H37Rv (virulent) strains. The effects on collagen synthesis, fibroblast proliferation and collagenase activity were examined. Matrix metalloproteinase-1 (MMP-1), MMP-13 and tissue inhibitors of metalloproteinases (TIMP-1) mRNA levels were analyzed by quantitative real-time PCR amplification. Protein expression was explored by Western blot technique. Results: Collagen synthesis and fibroblast proliferation were significantly increased by H37Ra medium. In contrast, cells incubated with H37Rv medium showed an increase in collagenase activity. MMPs quantitative real-time PCR amplification revealed an increase on MMP-13 mRNA levels in fibroblasts cultured with H37Rv medium, with little effect observed on MMP-1 expression. Western blot assay demonstrated that H37Rv medium stimulated MMP-1 and MMP-13 proenzyme synthesis. This medium had a large effect on MMP-1 activation. TIMP-1 transcription was increased in cells incubated with medium and sonicated from H37Ra, although the highest TIMP-1 protein expression was found in fibroblasts cultured with sonicated H37Rv. Conclusions: These results suggest that MTb had direct effects on fibroblast collagen turnover, with differences in collagen synthesis and degradation depending on the strain. Copyright (C) 2008 S. Karger AG, Basel