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Protection by nitric oxide against liver inflammatory injury in animals carrying a nitric oxide synthase‐2 transgene
Author(s) -
Mojena Marina,
Hortelano Sonsoles,
Castrillo Antonio,
DíazGuerra María J. M.,
GarcíaBarchino María J.,
Sáez Guillermo T.,
Boscá Lisardo
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0509fje
Subject(s) - proinflammatory cytokine , nitric oxide synthase , nitric oxide , lipopolysaccharide , liver injury , tumor necrosis factor alpha , phosphoenolpyruvate carboxykinase , chemistry , transgene , inflammation , pharmacology , medicine , endocrinology , biology , biochemistry , enzyme , gene
The effect of pre‐existent hepatic NO synthesis on liver injury induced by lipopolysaccharide was studied in animals carrying a nitric oxide synthase‐2 (NOS‐2) transgene under the control of the phosphoenolpyruvate carboxykinase (PEPCK) promoter. These animals expressed NOS‐2 in liver cells under fasting conditions. Lipopolysaccharide‐induced liver injury in D‐galactosamine‐conditioned mice, which enhanced notably the effect of the endotoxin on the liver, was impaired in animals expressing NOS‐2. This protection against inflammatory liver damage was dependent on NO synthesis and was caused by an inhibition of nuclear factor κB (NF‐κB) activity and an impairment of the synthesis of the proinflammatory cytokines tumor necrosis factor α and interleukin 1β. These data indicate that intrahepatic synthesis of NO protects liver by inhibiting the release of cascades of proinflammatory mediators and suggest a beneficial role for local delivery of NO in the control of liver injury.