title: Oncostatin M stimulates collagen and glycosaminoglycan production by cultured normal dermal fibroblasts: insensitivity of sclerodermal and keloidal fibroblasts.
abstract: It is thought that normal fibrotic repair progresses to dermal fibrosis when fibroblasts are activated persistently by chronic exposure to cytokines such as transforming growth factor-beta. However, additional cytokines and mechanisms may play a role in the development of fibrosis. Thus, we examined a recently described T-lymphocyte/macrophage-derived cytokine, oncostatin M, for its effect on the production of collagen and glycosaminoglycan by microcultures of normal dermal, sclerodermal, and keloidal fibroblasts. Treatment with oncostatin M for 48 h induced dose-dependent (1-100 ng/ml) increases in the collagen and glycosaminoglycan production of nine normal fibroblast strains, which in the absence of fetal bovine serum at 100 ng/ml averaged 196% and 244%, respectively. Oncostatin M treatment increased both types I and III procollagens and their mRNA transcripts, as well as levels of hyaluronic acid, chondroitin-4/6 sulfates, and dermatan sulfate, but not fibronectin or general noncollagenous protein synthesis. In contrast, the collagen production of six of eight sclerodermal and keloidal fibroblast strains was essentially unresponsive to oncostatin M treatment, with 100 ng/ml inducing an average increase of only 34% for the eight fibrotic strains. Oncostatin M stimulation of fibrotic fibroblast glycosaminoglycan production was also hyporesponsive, as 100 ng/ml of oncostatin M induced an average increase of only 101%. These results indicate that oncostatin M could function as a stimulator of normal fibrotic repair via activation of fibroblast collagen and glycosaminoglycan synthesis and that the persistent activation of sclerodermal and keloidal fibroblasts is accompanied by a loss of sensitivity to oncostatin M stimulation.
authors.affiliation: Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Florida.
authors.forename: M R
authors.initials: MR
authors.lastname: Duncan
authors.forename: A
authors.initials: A
authors.lastname: Hasan
authors.forename: B
authors.initials: B
authors.lastname: Berman
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006801:Humans; D007627:Keloid / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D011347:Procollagen / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012595:Scleroderma, Systemic / Q000473:pathology*
chemical_list: D006025:Glycosaminoglycans; C508351:OSM protein, human; D010455:Peptides; D011347:Procollagen; D012333:RNA, Messenger; D053683:Oncostatin M; D003094:Collagen