UP-REGULATION OF HEPATOCYTE GROWTH-FACTOR GENE-EXPRESSION BY INTERLEUKIN-1 IN HUMAN SKIN FIBROBLASTS

Hepatocyte growth factor (HGF) functions as a hepatotrophic and renotrophic factor for regeneration of the liver and kidney. When 1 ng/ml of interleukin-1α (IL-1α) or interleukin-1β (IL-1β) was added to cultures of human skin fibroblasts, the production of HGF was 5-6 fold higher than levels in the controls. HGF mRNA level in the cells was increased to 4-fold higher levels at 6 h after exposure to IL- 1α. Tumor necrosis factor-α and interferon-γ but no other cytokine tested had slightly stimulatory effects on HGF production. The tumor promoter, tetradecanoylphorbol 13-acetate (TPA) markedly enhanced the stimulatory effect of IL-1α and IL-1β on the production of HGF. The stimulatory effect of both IL-1α and IL-1β and the synergistical stimulation with TPA were completely abrogated by 10 ng/ml TGF-β 1 or 1 μM dexamethasone. These results suggest that IL-1α and IL-1β are positive regulators for expression of the HGF gene and are likely have a role in regeneration of tissues following the occurrence of inflammatory diseases. © 1992.