View article

—We tested the hypothesis that the inflammatory cytokines can regulate fibroblast extracellular matrix metabolism. Neonatal and adult rat cardiac fibroblasts cultures in vitro were exposed to interleukin (IL)–1β (4 ng/mL), tumor necrosis factor-α (TNF-α; 100 ng/mL), IL-6 (10 ng/mL), or interferon-γ (IFN-γ; 500 U/mL) for 24 hours. IL-1β, and to a lesser extent TNF-α, decreased collagen synthesis, which was measured as collagenase-sensitive [³H]proline incorporation, but had no effect on cell number or total protein synthesis. IL-1β decreased the expression of procollagen α₁(I), α₂(I), and α1(III) mRNA, but increased the expression of procollagen α₁(IV), α₂(IV), and fibronectin mRNA, indicating a selective transcriptional downregulation of fibrillar collagen synthesis. IL-1β and TNF-α each increased total matrix metalloproteinase (MMP) activity as measured by in-gel zymography, causing specific increases in the bands …