title: IL-1 beta stimulates superoxide and delayed peroxynitrite production by pulmonary vascular smooth muscle cells.
abstract: Our previous studies have shown that rat pulmonary microvascular smooth muscle cells (RPMSMC) upregulate inducible nitric oxide synthase (iNOS) and produce nitric oxide (NO) when treated with interleukin-1 beta (IL-1 beta). We now report that an additional effect of IL-1 beta stimulation in RPMSMC is an increase in production of superoxide (O2-) that results in the formation of peroxynitrite (ONOO-). IL-1 beta produced a rapid (within 1 h) concentration-dependent increase in O2-, as detected by ferricytochrome c reduction and lucigenin-enhanced chemiluminescence. O2- production was sensitive to quinacrine and diphenyliodinium, suggesting that NADH and NADPH oxidoreductases were responsible. After induction of iNOS and production of iNOS-derived NO, ONOO- was detected by luminol-enhanced chemiluminescence and was found to cause lipid peroxidation and to form nitrotyrosine in the cytoskeleton, detected by immunostaining. Cell viability, however, appeared to be unaffected. IL-1 beta-mediated induction of RPMSMC-derived ONOO- may have significant effects on pulmonary vascular function in sepsis and inflammatory states.
authors.affiliation: Department of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
authors.forename: A
authors.initials: A
authors.lastname: Boota
authors.forename: H
authors.initials: H
authors.lastname: Zar
authors.forename: Y M
authors.initials: YM
authors.lastname: Kim
authors.forename: B
authors.initials: B
authors.lastname: Johnson
authors.forename: B
authors.initials: B
authors.lastname: Pitt
authors.forename: P
authors.initials: P
authors.lastname: Davies
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation; D007375:Interleukin-1 / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism*; D051381:Rats; D013481:Superoxides / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D007375:Interleukin-1; D009566:Nitrates; D013481:Superoxides; C039642:peroxynitric acid