Opposite effects of tumour necrosis factor-α on type I and III collagen gene expression by human dermal fibroblasts in monolayer and three-dimensional cultures

✍ Scribed by Sato; Ishikawa; Abe; Miyachi

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 327 KB
• Volume: 138
• Category: Article
• ISSN: 0007-0963
• DOI: 10.1046/j.1365-2133.1998.02036.x

✦ Synopsis

We have recently established a novel fibroblast culture system supplemented with L-ascorbic acid 2-phosphate. The addition of L-ascorbic acid 2-phosphate enables human dermal fibroblasts to organize a three-dimensional dermis-like structure by accumulating collagens and extracellular matrices. The purpose of this study was to examine the effects of tumour necrosis factor-alpha (TNF-alpha) on collagen gene expression by human dermal fibroblasts in this culture system in comparison with monolayer culture. TNF-alpha suppressed the expression of pro alpha 1 (I) and pro alpha 1 (III) collagen mRNA in monolayer culture. In contrast, their expression was elevated in the three-dimensional culture system. TNF-alpha increased the mRNA expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 both in monolayer and three-dimensional culture. These data suggest that responses of human dermal fibroblasts to TNF-alpha are distinct under the different culture conditions. Extracellular matrices may modulate the responsiveness of fibroblasts to TNF-alpha.