Antioxidative role of interleukin-6 in septic lung injury in mice.
We have previously demonstrated the protective role of interleukin (IL)-6 against septic lung injury induced by lipopolysaccharide (LPS) using IL-6 knock-out (-/-) mice. This protection is mediated, at least partly, through the inhibition of the enhanced local expression of proinflammatory cytokines. In the present study, we addressed whether IL-6 regulates oxidative stress in the lung generated by LPS exposure using IL-6 (-/-) and corresponding wild type (WT) mice. Intraperitoneal LPS (1 mg/kg) challenge induced transcriptional expressions of inducible nitric oxide synthase and heme oxygenase -1 in the lung of mice with both genotypes. In the presence of LPS, these expressions were significantly greater in IL-6 (-/-) than in WT mice. Immunohistochemistry also showed that LPS induced a significant increase in 8-hydroxy-2'-deoxyguanosine formation in the lung as compared to vehicle. Furthermore, the formation was more intense in IL-6 (-/-) than in WT mice in the presence of LPS challenge. In the presence of LPS, lipid peroxidation in the lung was significantly greater in IL-6 (-/-) than in WT mice. These data suggest that the possible mechanisms in which endogenous IL-6 protects against septic lung injury induced by LPS involve, at least in part, its antioxidative properties.
Inoue
K
K
Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan. inoue.kenichirou@nies.go.jp
Takano
H
H
Yanagisawa
R
R
Sakurai
M
M
Shimada
A
A
Satoh
M
M
Yoshino
S
S
Yamaki
K
K
Yoshikawa
T
T
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000502:physiology*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D051547:Heme Oxygenase-1 / Q000235:genetics; D015850:Interleukin-6 / Q000502:physiology*; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D018805:Sepsis / Q000378:metabolism*
D000975:Antioxidants; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000080242:8-Hydroxy-2'-Deoxyguanosine; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D003849:Deoxyguanosine