INTERLEUKIN-1-BETA PREVENTS THE STIMULATORY EFFECT OF TRANSFORMING GROWTH-FACTOR-BETA ON COLLAGEN GENE-EXPRESSION IN HUMAN SKIN FIBROBLASTS

Transforming growth factors β1 and β2 (TGF-β1 and TGF-β2) are well-characterized strong inducers of collagen gene expression. A 100 pM concentration of TGF-β1 or TGF-β2 increases proα1(I) collagen mRNA levels in human skin fibroblasts 6.6-fold and 7.0-fold respectively, and also increases the accumulation of procollagens in the cell culture medium. Interleukin-1β (IL-1β) is an inflammatory mediator which also regulates connective tissue metabolism. A small concentration of IL-1β (0.01-1.0 unit/ml) slightly increases proα1(I) collagen mRNA levels (2.2-fold). Here we provide evidence that IL-1β prevents the stimulatory effect of TGFs-β on collagen synthesis in human skin fibroblasts. An IL-1β concentration of 1 unit/ml is enough to keep proα1(I) collagen mRNA levels at control values in cells stimulated by 100 pM-TGF-β1. Thus the results indicate that IL-1β inhibits collagen synthesis in cells activated by TGFs-β, whereas it does not significantly change or might even stimulate collagen gene expression in non-activated cells.