Figure 7.
CoMTb induces MMP-1 secretion from fibroblasts via cytokine-dependent networks. (A) MMP-1 induction is TNF-α– and IL-1–dependent. CoMTb was pre-incubated for 2 hours with anti–TNF-α antibody (μg/ml) before stimulating MRC5 cells. For IL-1 inhibition, cells were pretreated with IL-1Ra (ng/ml) for 2 hours before stimulation with CoMTb for 72 hours. MMP-1 was measured by casein zymography. (B) OSM inhibition reduces MMP-1 secretion. CoMTb was pre-incubated with anti-OSM antibody (μg/ml) for 2 hours before stimulation of MRC5 cells. MMP-1 was measured by casein zymography. Data are expressed as fraction of that induced by CoMTb at 72 hours (CoMTb = 1), *P < 0.05 compared with CoMTb. (C) TNF-α, IL-1β, and OSM induce p38 phosphorylation. MRC5 cells were stimulated with TNF-α, IL-1β, OSM (all 10 ng/ml) for 30 minutes, and lysates probed for phosphorylated and total p38. (D) OSM phosphorylates STAT1 and 3. Western blots of lysates harvested at 30 minutes are shown.