SCLERODERMA FIBROBLAST PHENOTYPE IS MODULATED BY ENDOTHELIAL-CELL COCULTURE

Objective. We established a co-culture system to investigate endotheli al cell-fibroblast interaction in scleroderma (systemic sclerosis, SSc ). Such a system allows reciprocal interaction between these cells. Th e pattern of phenotypic modulation for normal and SSc fibroblasts in c o-culture was compared. Methods. A virally transformed human umbilical vein endothelial cell (HUVEC) derived cell line (1E-7) was cultured o n nitrocellulose membrane inserts above dermal fibroblast monolayers. The effect of co-culture on fibroblast number, [H-3]-thymidine ([H-3]- TdR) incorporation, and collagen (type I) production were compared for 10 SSc and 5 control cell lines. Co-culture with the epithelial lines A549 and A431, and nontransformed HUVEC, was also investigated. Resul ts. We observed a statistically significant increase in cell number an d a reduction in collagen production for SSc, but not control, fibrobl asts co-cultured with endothelial cells. This co-culture also promoted [H-3]-TdR incorporation in both SSc and control fibroblasts. While ep ithelial cell lines did not influence fibroblast cell number, collagen production by SSc fibroblasts was diminished by A549. Conclusion. End othelial cell derived soluble factors modulate fibroblast properties i n co-culture, and the different response of SSc compared with normal f ibroblasts provides further evidence for a link between endothelial an d fibroblast dysfunction in this disease. However, similar effects on SSc fibroblast collagen production were also observed for some epithel ial cells, suggesting that modulation of fibroblast properties is not restricted to cells of endothelial origin.