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

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.

journal_name

Arch Dermatol Res

authors

Takeda K,Hatamochi A,Arakawa M,Ueki H

doi

10.1007/BF00373353

subject

Has Abstract

pub_date

1993-01-01 00:00:00

pages

440-4

issue

8

eissn

0340-3696

issn

1432-069X

journal_volume

284

pub_type

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