Antioxidative role of urinary trypsin inhibitor in acute lung injury induced by lipopolysaccharide.
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.
Inoue
Ken-Ichiro
K
Environmental Health Sciences Division, National Institute for Environmental Studies, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Takano
Hirohisa
H
Yanagisawa
Rie
R
Sakurai
Miho
M
Shimada
Akinori
A
Sato
Hiroyuki
H
Kato
Yoji
Y
Yoshikawa
Toshikazu
T
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
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