Growth regulation of cultured endothelial cells by inflammatory cytokines: mitogenic, anti-proliferative and cytotoxic effects.
The inflammatory cytokines tumor necrosis factor-alpha (TNF alpha) and interleukin-1 alpha (IL-1 alpha) have angiogenic properties but generally inhibit cultured endothelial cell (EC) proliferation. Investigations into the growth-regulatory effects of these two agents on a variety of cultured EC types showed that they exert mitogenic, anti-proliferative or cytotoxic effects depending upon cell type and cytokine combinations. The anti-proliferative effect was distinct from cytotoxicity. Nitric oxide (NO) release from EC, examined as a potential mechanism underlying some of these effects, did not appear to mediate the anti-proliferative effects of these cytokines. However, NO also seemed to have a bimodal effect on EC proliferation depending upon whether the NO was endogenous or exogenous. These data underscore the diversity in cytokine and NO effects on cultured EC which, if reproducible in vivo, may be partly responsible for the variable and sometimes contradictory results obtained with regards to the role of inflammatory cytokines and NO on angiogenesis.
Gerol
M
M
Department of Pharmacology, Rush Medical College, Chicago, IL 60612, USA.
Curry
L
L
McCarroll
L
L
Doctrow
S
S
RayChaudhury
A
A
D000818:Animals; D001921:Brain / Q000098:blood supply; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008934:Mitogens / Q000494:pharmacology*; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000032:analysis; D011651:Pulmonary Artery; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D008934:Mitogens; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D009569:Nitric Oxide