OPPOSITE EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA ON TYPE-I AND TYPE-III COLLAGEN GENE-EXPRESSION BY HUMAN DERMAL FIBROBLASTS IN MONOLAYER AND 3-DIMENSIONAL CULTURES

We have recently established a novel fibroblast culture system supplem ented with L-ascorbic acid 2-phosphate, The addition of L-ascorbic aci d 2-phosphate enables human dermal fibroblasts to organize a three-dim ensional dermis-like structure by accumulating collagens and extracell ular 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 contras t, their expression was elevated in the three-dimensional culture syst em, TNF-alpha. increased the mRNA expression of matrix metalloproteina se-1 and tissue inhibitor of metalloproteinase-l both in monolayer and three-dimensional culture, These data suggest that responses of human dermal fibroblasts to TNF-alpha are distinct under the different cult ure conditions, Extracellular matrices may modulate the responsiveness of fibroblasts to TNF-alpha.