Interleukin 1 is an autocrine regulator of human endothelial cell growth.
Proliferation of endothelial cells is regulated through the autocrine production of growth factors and the expression of cognate surface receptors. In this study, we demonstrate that interleukin 1 (IL-1) is an inhibitor of endothelial growth in vitro and in vivo. IL-1 arrested growing, cultured endothelial cells in G1 phase; inhibition of proliferation was dose dependent and occurred in parallel with occupancy of endothelial surface IL-1 receptors. In an angiogenesis model, IL-1 could inhibit fibroblast growth factor-induced vessel formation. The autocrine nature of the IL-1 effect on endothelial proliferation was demonstrated by the observation that occupancy of cell-surface receptors by endogenous IL-1 depressed cell growth. The potential significance of this finding was emphasized by the detection of IL-1 in the native endothelium of human umbilical veins. A mechanism by which IL-1 may exert its inhibitory effect on endothelial cell growth was suggested by studies showing that IL-1 decreased the expression of high-affinity fibroblast growth factor binding sites on endothelium. These results point to a potentially important role of IL-1 in regulating blood vessel growth and suggest that autocrine production of inhibitory factors may be a mechanism controlling proliferation of normal cells.
Istituto di Clinica Medica IV, Università di Firenze, Florence, Italy.
F
F
Cozzolino
M
M
Torcia
D
D
Aldinucci
M
M
Ziche
F
F
Almerigogna
D
D
Bani
D M
DM
Stern
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D009389:Neovascularization, Pathologic; D011817:Rabbits; D011971:Receptors, Immunologic / Q000378:metabolism; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
D007375:Interleukin-1; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D005346:Fibroblast Growth Factors; D004247:DNA