Induction of MMP-9 mediated gelatinolytic activity in human monocytic cells by cell wall components of Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) infection induces the expression of host m atrix metalloproteinases (MMPs) capable of tissue degradation. We show that infection of mice with Mtb results in differential expression of MMPs in t he lung. MMP-9 activity increased by week 1 post-infection, while MMP-2 act ivity increased after week 2. RT-PCR analysis for gene expression of gelati nases and their respective inhibitors showed: a small increase in MMP-9 by week 1, no change in TIMP-1 and MMP-2, and a significant decrease in TIMP-2 by week 4. The increase in MMP-2 could be due to a decrease in TIMP-2 expr ession. Addition of 4-aminophenylmercuric acid to lung extracts increased M MP-9 activity, suggesting that its regulation could be due to endogenous ac tivation by proteases. in vitro, attenuated and virulent Mtb strains equall y induced MMP-9 expression in U937 monocytes. The inducer of MMP-9 in Mtb w as present in culture filtrates, and was active after paraformaldehyde fixa tion. LAM stimulated MMP-9 expression in THP-1 cells, but not U937 cells. H owever, LAM-free extracts also induced MMP-9 activity in THP-1 cells. Fract ionation of Mtb extracts by chromatography revealed fractions of 17 and 156 kDa with MMP-9 inducing activity. In conclusion, LAM and other components of Mtb induce the expression of MMP-9.