title: Role of NO in enhancing the expression of HO-1 in LPS-stimulated macrophages.
abstract: Macrophages serve as the first-line defense against invading pathogens by (a) overproducing O2- via activation of NADPH-oxidase localized in its plasma membrane, (b) inducing the expression of inducible nitric oxide synthase (iNOS) and overproducing NO, and (c) generating highly toxic peroxynitrite (ONOO-) to kill the invading pathogens without killing the macrophages themselves. Results show that this was due at least in part to the NO-derived induction of heme oxygenase-1 (HO-1) expression. The NO-derived induction of HO-1 caused (a) rapid elimination of toxic heme to inhibit lipid peroxidation and to prevent further induction of iNOS, (b) rapid production of bile pigment antioxidants to scavenge reactive oxygen (O2-) and nitrogen (NO) metabolites, and (c) rapid production of carbon monoxide (CO) to inhibit further production of O2- and NO by blocking the activities of NADPH-oxidase and iNOS, respectively. Thus, the NO overproduced by the O2- -dependent induction of iNOS expression can scavenge O2- to produce ONOO-, first to kill the invading pathogens and second to enhance the HO-1 expression in macrophages. This allows the survival of host tissues from the injuries caused by inflammatory oxidative stress.
authors.affiliation: Department of Pharmacology and Toxicology, Medicinal Toxicology Center, College of Medicine, Inha University, Inchon, South Korea.
authors.forename: Klaokwan
authors.initials: K
authors.lastname: Srisook
authors.forename: Chaekyun
authors.initials: C
authors.lastname: Kim
authors.forename: Young-Nam
authors.initials: YN
authors.lastname: Cha
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D018384:Oxidative Stress
chemical_list: D008070:Lipopolysaccharides; D009569:Nitric Oxide; D006419:Heme Oxygenase (Decyclizing)