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Tumor necrosis factor inhibits collagen and fibronectin synthesis in human dermal fibroblasts
A Mauviel1, M Daireaux, F Rédini
1Laboratoire de Biochimie du Tissu Conjonctif, CHU Côte de Nacre, Caen, France.
Abstract:
Tumor necrosis factor (TNF) caused inhibition of collagen production by confluent cultures of human dermal fibroblasts in a dose-dependent manner. Concomitant increase of prostaglandin E2 release was observed as a result of TNF-induced cell activation. However, a blockade of the cyclooxygenase pathway of arachidonate metabolism by indomethacin did not abrogate the inhibitory effect of TNF on collagen synthesis, suggesting that this effect could be independent of prostaglandin metabolism. Gel electrophoresis of the newly synthesized macromolecules from the culture media showed that both type I and type III collagens as well as fibronectin were affected by the inhibition. Electrophoresis of cell layer-associated proteins demonstrated that the reduction in amounts of collagen and fibronectin in the medium did not result from an intracellular accumulation of these macromolecules. Production of procollagens was reduced in parallel to that of collagens, suggesting that the effect of TNF is exerted before the processing steps of procollagens. These results clearly show that TNF could play a role in modulation of matrix deposition by fibroblasts during inflammatory processes.
Insights
Tumor necrosis factor (TNF) inhibits fibroblast collagen production, impacting matrix deposition during inflammation. This effect is independent of prostaglandin E2, suggesting a direct role for TNF in modulating extracellular matrix synthesis.
Area of Science:
- Dermatology
- Cell Biology
- Inflammation Research
Background:
- Fibroblasts are crucial for producing extracellular matrix components like collagen.
- Inflammatory processes can alter fibroblast function and matrix deposition.
- Tumor necrosis factor (TNF) is a key inflammatory cytokine.
Purpose of the Study:
- To investigate the effect of TNF on collagen production by human dermal fibroblasts.
- To determine the role of prostaglandin E2 in TNF-mediated collagen inhibition.
- To elucidate the mechanism by which TNF affects collagen synthesis.
Main Methods:
- Culturing human dermal fibroblasts.
- Treating cultures with varying doses of TNF.
- Measuring collagen and fibronectin synthesis.
- Assessing prostaglandin E2 release.
- Utilizing gel electrophoresis to analyze protein synthesis.
- Investigating the effect of indomethacin (cyclooxygenase inhibitor).
Main Results:
- TNF dose-dependently inhibited collagen production in fibroblasts.
- TNF increased prostaglandin E2 release, but indomethacin did not block collagen inhibition.
- Both type I and type III collagens, along with fibronectin, were reduced.
- Inhibition affected procollagen production, indicating an early mechanism.
- No intracellular accumulation of collagen or fibronectin was observed.
Conclusions:
- TNF directly inhibits collagen and fibronectin synthesis in dermal fibroblasts.
- The inhibitory effect of TNF on collagen production is independent of prostaglandin metabolism.
- TNF plays a significant role in regulating fibroblast matrix deposition during inflammation.