title: Lipopolysaccharide-induced overproduction of nitric oxide and overexpression of iNOS and interleukin-1β proteins in zinc-deficient rats.
abstract: Zinc deficiency leads to decreased cellular immune responses. The overproduction of nitrogen species derived from inducible nitric oxide synthase (iNOS), its enzyme, and interleukine-1 beta (IL-1β), and inflammatory cytokine have been implicated in immune responses. The goal of this study was to investigate the effects of lipopolysaccharide (LPS)-induced changes in NO metabolites, iNOS, and IL-1β protein expression in the lungs of zinc-deficient rats. Male Sprague-Dawley rats (body weight, 100 g) were divided into two groups and were fed either a zinc-deficient diet (ZnD) or a zinc-containing diet (Cont). After 4 weeks on these diets, rats received a 10-mg/kg dose of LPS injected via the tail vein and were then maintained for an additional 72 h. To determine total NO concentrations in the blood, serum zinc concentration, iNOS protein expression, IL-1β, and iNOS immunohistochemistry, blood and lung samples were obtained at pre-LPS injection, 5, 24, and 72 h after injection. Total NO levels were significantly increased at 5, at 24, and at 72 h after LPS injection compared with pre-LPS injection level in ZnD group; significant changes in total NO levels was elevated at 5 h from at pre-LPS level but not significant changes from basal level at 24 and 72 h in the control group. Based on western blot analyses and immunohistochemistry, clear bands indicating iNOS and IL-1β protein expression and iNOS antibody-stained inflammatory cells were detected at 5 and 24 h in the ZnD group and 5 h in the Cont group, not observed at 24 and 72 h in the control group. These results suggest that zinc deficiency induces overexpression of iNOS and IL-1β proteins from inflammatory cells around the alveolar blood vessels, resulting in overproduction of total NO and persisted inflammatory response in the zinc-deficient rat lung. Taken together, overexpression of LPS-induced iNOS, overproduction of iNOS-derived NO, and overexpression of IL-1β may induce nitrosative and oxidative stresses in the lung, and these stresses may be involved low immunity of zinc deficiency states.
authors.affiliation: Community Health Science Center, Saitama Medical University, 38 Moro-hongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan. miyasan@saitama-med.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Takenaka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Inoue
authors.forename: Makiko
authors.initials: M
authors.lastname: Sato
authors.forename: Yuka
authors.initials: Y
authors.lastname: Miyajima
authors.forename: Makoto
authors.initials: M
authors.lastname: Nodera
authors.forename: Mayuko
authors.initials: M
authors.lastname: Hanyu
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ohno
authors.forename: Satomi
authors.initials: S
authors.lastname: Shibazaki
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D015153:Blotting, Western; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015032:Zinc / Q000097:blood / Q000172:deficiency*
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D015032:Zinc