Interleukin 1 regulates heparin-binding growth factor 2 gene expression in vascular smooth muscle cells

The angiogenic polypeptide heparin-binding growth factor 2 (HBGF-2), or basic fibroblast growth factor, is a mitogen for vascular smooth muscle cells in vitro and in vivo. Smooth muscle cells also synthesize HBGF-2; thus, it may stimulate their proliferation in vivo by both autocrine and paracrine mechanisms. We report here that HBGF-2 gene expression in human saphenous vein smooth muscle cells is induced by interleukin (IL)-1 alpha and IL-1 beta, inflammatory cytokines produced by many cell types in response to a variety of signals. Maximal HBGF-2 mRNA levels are detected 2-4 hr after IL-1 treatment; induction may require de novo protein synthesis and does not occur if transcription is inhibited. Immunoprecipitation analysis indicates that IL-1-stimulated cells also express an increased amount of HBGF-2 protein. Interferon gamma and glucocorticoids, inhibitors of smooth muscle cell proliferation in vitro and in vivo, suppress the induction of HBGF-2 expression by IL-1. These results imply that cytokines released at sites of vascular injury or inflammation may regulate HBGF-2 production by smooth muscle cells. Increased HBGF-2 levels within the vessel wall could play a role in both the smooth muscle cell proliferation and the neovascularization associated with the development of atherosclerotic lesions.