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.
Gay
C G
CG
Laboratory of Molecular Biology, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, MD 20855.
Winkles
J A
JA
D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000235:genetics / Q000494:pharmacology*; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000494:pharmacology; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D003609:Dactinomycin; D003907:Dexamethasone; D007371:Interferon-gamma; D003513:Cycloheximide; D006854:Hydrocortisone