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Effects of tumor necrosis factor-α on connective tissue metabolism in normal and scleroderma fibroblast cultures

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Abstract

Recent studies have demonstrated that tumor necrosis factor-α(TNF-α) 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-α 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-α 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 α1(VI) and α3(VI) collagen and for Β-actin were unaltered in SSc fibroblasts incubated with TNF-α. Similar results were observed for mRNA levels in normal fibroblasts incubated with TNF-α. These results suggest that TNF-α 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-α.

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Authors and Affiliations

  1. Department of Dermatology, Kawasaki Medical School, 577 Matsushima, 701-01, Kurashiki, Japan

    K. Takeda, A. Hatamochi, M. Arakawa & H. Ueki

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  1. K. Takeda
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  2. A. Hatamochi
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  3. M. Arakawa
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  4. H. Ueki
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Takeda, K., Hatamochi, A., Arakawa, M. et al. Effects of tumor necrosis factor-α on connective tissue metabolism in normal and scleroderma fibroblast cultures. Arch Dermatol Res 284, 440–444 (1993). https://doi.org/10.1007/BF00373353

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  • DOI: https://doi.org/10.1007/BF00373353

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