Modulation of the organization of the extracellular matrix and the production of collagen by interferon gamma in three-dimensional cultures of normal and sclerodermic fibroblasts
Serpier, H.; Gillery, P.; Polette, M.; Clavel, C.; Birembaut, P.; Kalis, B.; Cariou, R.; Maquart, F.X.
Pathologie-Biologie 40(9): 865-870
1992
ISSN/ISBN: 0369-8114 PMID: 1296158 Document Number: 402690
Recent studies have shown inhibition of collagen synthesis by interferon gamma (IFN-gamma) in monolayer human fibroblast cultures on a plastic solid phase. However, the existence of this effect in vivo has not yet been demonstrated. Three-dimensional fibroblast cultures in collagen matrices (collagen lattices or dermal equivalents) provide a more physiological model than conventional cultures and fairly closely simulate in vivo conditions. This model was used for studying effects of IFN-gamma on normal and scleroderma fibroblasts. IFN-gamma induced a dose-dependent inhibition of fibroblast-mediated retraction of collagen lattices. IFN-gamma also inhibited total protein and collagen synthesis. Scleroderma fibroblasts were especially susceptible to the inhibitory effects of IFN-gamma. Since fibrotic scleroderma lesions are associated with tissue retraction and increased production of extracellular matrix macromolecules, these data confirm the potential value of IFN-gamma for the treatment of scleroderma and other fibrotic diseases.