ONCOSTATIN-M STIMULATES COLLAGEN AND GLYCOSAMINOGLYCAN PRODUCTION BY CULTURED NORMAL DERMAL FIBROBLASTS - INSENSITIVITY OF SCLERODERMAL ANDKELOIDAL FIBROBLASTS
Mr. Duncan et al., ONCOSTATIN-M STIMULATES COLLAGEN AND GLYCOSAMINOGLYCAN PRODUCTION BY CULTURED NORMAL DERMAL FIBROBLASTS - INSENSITIVITY OF SCLERODERMAL ANDKELOIDAL FIBROBLASTS, Journal of investigative dermatology, 104(1), 1995, pp. 128-133
It is thought that normal fibrotic repair progresses to dermal fibrosi
s when fibroblasts are activated persistently by chronic exposure to c
ytokines such as transforming growth factor-beta. However, additional
cytokines and mechanisms may play a role in the development of fibrosi
s. Thus, we examined a recently described T-lymphocyte/macrophage-deri
ved cytokine, oncostatin M, for its effect on the production of collag
en and glycosaminoglycan by microcultures of normal dermal, scleroderm
al, and keloidal fibroblasts. Treatment with oncostatin M for 48 h ind
uced dose-dependent (1-100 ng/ml) increases in the collagen and glycos
aminoglycan production of nine normal fibroblast strains, which in the
absence of fetal bovine serum at 100 ng/ml averaged 196% and 244%, re
spectively. Oncostatin M treatment increased both types I and III proc
ollagens and their mRNA transcripts, as well as levels of hyaluronic a
cid, chondroitin-4/6 sulfates, and dermatan sulfate, but not fibronect
in or general noncollagenous protein synthesis. In contrast, the colla
gen production of six of eight sclerodermal and keloidal fibroblast st
rains 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 glycosaminog
lycan 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 fibro
blasts is accompanied by a loss of sensitivity to oncostatin M stimula
tion.