Protective role of urinary trypsin inhibitor in lung expression of proinflammatory cytokines accompanied by lethal liver injury in mice.
Urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely used for patients with inflammatory disorders including disseminated intravascular coagulation, shock, and pancreatitis in Japan, since it reportedly exhibits anti-inflammatory properties aside from its blocking of the protease pathway both in vitro and in vivo. In accordance with other reports, our previous studies using UTI-null (-/-) mice showed that UTI protects against systemic inflammatory responses in vivo. Recently, we also revealed the protective role of UTI against lethal liver injury induced by lipopolysaccharide and D-galactosamine (LPS/D-GalN). However, the anti-inflammatory role of UTI has not been sufficiently clarified using the model. The present study determined the effects of endogenous UTI on lung inflammation accompanied by lethal liver injury induced by LPS/D-GalN in the context of the lung expression of proinflammatory cytokines. After LPS/D-GalN challenge, protein levels of interleukin-1beta, tumor necrosis factor-alpha, macrophage inflammatory protein-1alpha, and macrophage chemoattractant protein-1 in the lung homogenates were elevated in both genotypes, but to a greater extent in UTI (-/-) than in WT mice (P < 0.05 for TNF-alpha). The IFN-gamma level was also significantly greater in LPS/D-GalN challenged UTI (-/-) mice than in other mice (P < 0.01). These results suggest that UTI protects against the local inflammatory response accompanied by severe liver injury, which supports its anti-inflammatory properties in vivo.
Inoue
Ken-ichiro
K
Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Japan. inoue.kenichirou@nies.go.jp
Takano
Hirohisa
H
Sato
Hiroyuki
H
Yanagisawa
Rie
R
Yoshikawa
Toshikazu
T
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D005688:Galactosamine / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout
D016207:Cytokines; D006023:Glycoproteins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D005688:Galactosamine; C028665:urinastatin