Takeda K, Hatamochi A, Arakawa M, Ueki H
Department of Dermatology, Kawasaki Medical School, Kurashiki, Japan.
Arch Dermatol Res. 1993;284(8):440-4. doi: 10.1007/BF00373353.
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.
最近的研究表明，肿瘤坏死因子-α（TNF-α）可选择性降低真皮中主要胶原类型Ⅰ型和Ⅲ型胶原的生成，并增加培养的真皮成纤维细胞中胶原酶的生成。研究了TNF-α对正常个体和系统性硬化症（SSc）患者来源的成纤维细胞中Ⅰ型、Ⅲ型和Ⅵ型胶原、纤连蛋白及胶原酶基因表达的影响。SSc的特征是皮肤和某些器官中胶原过度蓄积。TNF-α抑制SSc成纤维细胞中Ⅰ型和Ⅲ型胶原以及纤连蛋白的胶原生成和mRNA水平，并刺激胶原酶活性和胶原酶mRNA水平。在与TNF-α孵育的SSc成纤维细胞中，α1（Ⅵ）和α3（Ⅵ）胶原以及β-肌动蛋白的mRNA水平未发生改变。在用TNF-α孵育的正常成纤维细胞中，mRNA水平也观察到类似结果。这些结果表明，TNF-α有望对SSc的治疗有益。此外，我们的结果表明，Ⅵ型胶原的表达独立于Ⅰ型和Ⅲ型胶原的表达，在用TNF-α处理的成纤维细胞中，纤连蛋白以及Ⅰ型和Ⅲ型胶原的表达是平行调节的。
