Keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) are fibroblast-derived mitogens. KGF is a potent mitogen for epithelial cells but lacks corresponding activity on fibroblasts or other nonepithelial cells. HGF is a broad spectrum mitogen with activity on endothelial cells and melanocytes as well as epithelial cells. Results demonstrated that KGF and HGF are widely expressed among different types of human stromal fibroblasts such as embryonic lung, foreskin, adult skin and prostate fibroblasts. The effect of several cytokines in the induction of HGF and KGF mRNA in human embryonic lung and adult skin fibroblasts was examined. IL-1alpha, TGFalpha, bFGF and IL-6 elevated the levels of HGF mRNA in fibroblasts as well as smooth muscle cells. TGFalpha, PDGF-BB and IL-1alpha significantly increased the levels of KGF mRNA. The mechanism by which IL-1alpha elevated KGF mRNA expression was further studied. IL-1alpha increased KGF mRNA expression in time and dose-dependent manners by stimulating the rate of transcription of the KGF gene. This effect was significantly reduced by anti-IL-1 antibodies. Corresponding levels of KGF protein were detected in the supernatant of IL-1-stimulated cells. Mitogenic assays indicated that KGF present in the conditioned medium from IL-1-stimulated cells can support the growth of human primary keratinocytes.
