Opposite effects of tumour necrosis factor-alpha on type I and III collagen gene expression by human dermal fibroblasts in monolayer and three-dimensional cultures.
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.
Sato
M
M
Department of Dermatology, Gunma University School of Medicine, Japan.
Ishikawa
O
O
Abe
M
M
Miyachi
Y
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015152:Blotting, Northern; D018929:Cell Culture Techniques / Q000379:methods; D002648:Child; D002675:Child, Preschool; D017364:Collagenases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1; D010446:Peptide Fragments / Q000378:metabolism; D011347:Procollagen / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D010446:Peptide Fragments; D011347:Procollagen; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; C042813:procollagen type I carboxy terminal peptide; D017364:Collagenases; D020781:Matrix Metalloproteinase 1