Figure 4. M. tuberculosis upregulates MMP-1 secretion and activity, which is inhibited by Ro32-3555.

(A) M. tuberculosis–upregulated MMP1 gene expression causes increased secretion. Infected monocytes secreted 46-fold more MMP1 at 24 hours than uninfected cells. Monocyte stimulation with 3 μm latex beads did not upregulate MMP1 secretion, but stimulation with UV-killed TB and the synthetic TLR-2 ligand Pam₃Cys upregulated MMP1 equivalently to live M. tuberculosis. Secretion of other MMPs by infected monocytes is shown in Supplemental Figure 3. (B) M. tuberculosis infection, but not TB supernatant (TB sup), causes increased monocyte migration across a Matrigel-coated transwell system, demonstrating that increased MMP secretion causes greater extracellular matrix degradation. (C) MMP-1 activity secreted by M. tuberculosis–infected human macrophages is completely inhibited by 10 nM Ro32-3555, analyzed by casein zymography. Std, human MMP-1 standard 5 ng. ***P < 0.001.