title: Antioxidative role of urinary trypsin inhibitor in acute lung injury induced by lipopolysaccharide.
abstract: We have previously demonstrated the protective role of urinary trypsin inhibitor (UTI) against acute inflammatory lung injury induced by lipopolysaccharide (LPS) using UTI-deficient (-/-) mice and corresponding wild-type (WT) mice. The protection was mediated, at least partly, through inhibition of the enhanced local expression of proinflammatory cytokines, chemokines, and intercellular adhesion molecule-1. In the present study, we addressed whether UTI regulates oxidative stress generated by LPS challenge in the lung. UTI (-/-) and WT mice were treated intratracheally with vehicle or LPS (125 microg/kg). After LPS challenge in both genotypes of mice, the lung levels of mRNA for inducible nitric oxide synthase and hemo oxygenase-1 were elevated, but to a greater extent in UTI (-/-) mice than in WT mice. Immunohistochemistry showed that the formations of 8-hydroxy-2'-deoxyguanosine and nitrotyrosine in the lung were more intense in UTI (-/-) mice than in WT mice after LPS challenge. These results indicate that endogenous UTI is protective against acute lung injury induced by bacterial endotoxin, at least partly, via the antioxidative properties.
authors.affiliation: Environmental Health Sciences Division, National Institute for Environmental Studies, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Inoue
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
authors.forename: Rie
authors.initials: R
authors.lastname: Yanagisawa
authors.forename: Miho
authors.initials: M
authors.lastname: Sakurai
authors.forename: Akinori
authors.initials: A
authors.lastname: Shimada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sato
authors.forename: Yoji
authors.initials: Y
authors.lastname: Kato
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D015870:Gene Expression; D006023:Glycoproteins / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000975:Antioxidants; D006023:Glycoproteins; D008070:Lipopolysaccharides; C002744:3-nitrotyrosine; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D003849:Deoxyguanosine; C028665:urinastatin