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Effects of tumor necrosis factor-alpha on connective tissue metabolism in normal and scleroderma fibroblast cultures
K Takeda1, A Hatamochi, M Arakawa
1Department of Dermatology, Kawasaki Medical School, Kurashiki, Japan.
Abstract:
Recent studies have demonstrated that tumor necrosis factor-alpha (TNF-alpha) selectively decreases production of collagens I and III, the major types of collagen in the dermis, and increases production of collagenase in cultured dermal fibroblasts. The effects of TNF-alpha on collagens I, III and VI, fibronectin and collagenase gene expression by fibroblasts derived from normal individuals and patients with systemic sclerosis (SSc) were studied. SSc is characterized by excessive accumulation of collagen in the skin and in certain organs. TNF-alpha inhibited collagen production and mRNA levels of collagens I and III and of fibronectin, and stimulated collagenase activity and collagenase mRNA levels in SSs fibroblasts. Levels of mRNA for alpha 1 (VI) and alpha 3 (VI) collagen and for beta-actin were unaltered in SSc fibroblasts incubated with TNF-alpha. Similar results were observed for mRNA levels in normal fibroblasts incubated with TNF-alpha. These results suggest that TNF-alpha could be expected to be beneficial in the treatment of SSc. In addition, our results indicated that collagen-VI expression is regulated independently from expression of collagens I and III, and expression of fibronectin and collagens I and III are regulated in parallel in fibroblasts treated with TNF-alpha.
Insights
Tumor necrosis factor-alpha (TNF-alpha) reduces collagen production in systemic sclerosis (SSc) fibroblasts, suggesting potential therapeutic benefits for SSc treatment. This finding highlights TNF-alpha's role in regulating extracellular matrix components.
Area of Science:
- Dermatology
- Immunology
- Molecular Biology
Background:
- Systemic sclerosis (SSc) is marked by excessive collagen accumulation in the skin.
- Tumor necrosis factor-alpha (TNF-alpha) influences collagen and matrix metalloproteinase production in fibroblasts.
Purpose of the Study:
- To investigate the effects of TNF-alpha on collagen types I, III, VI, fibronectin, and collagenase gene expression in fibroblasts from normal individuals and SSc patients.
- To assess the potential of TNF-alpha as a therapeutic agent for SSc.
Main Methods:
- Cultured dermal fibroblasts from normal individuals and SSc patients were treated with TNF-alpha.
- Gene expression levels for collagens I, III, VI, fibronectin, and collagenase were analyzed using mRNA analysis.
- Collagenase activity was also measured.
Main Results:
- TNF-alpha inhibited collagen I, III, and fibronectin production and mRNA levels in SSc fibroblasts.
- TNF-alpha stimulated collagenase activity and mRNA levels in SSc fibroblasts.
- Collagen VI mRNA levels (alpha 1 and alpha 3) and beta-actin mRNA were unaffected by TNF-alpha in both normal and SSc fibroblasts.
Conclusions:
- TNF-alpha demonstrates potential as a beneficial treatment for SSc by reducing excessive collagen deposition.
- Collagen VI expression is regulated independently of collagens I and III.
- Fibronectin and collagen I/III expression are coordinately regulated by TNF-alpha in fibroblasts.
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