The stress-inducible protein @entity10183 provides protection against oxidative stress and modulates pro-inflammatory cytokines. As the @entity1850 results from the release of pro-inflammatory mediators, we postulated that @entity10183 and its enzymatic product CO would protect against lethality in a @entity19 model of @entity295 . @entity19 treated with a lethal dose of lipopolysaccharide (LPS) and subsequently exposed to inhaled CO had significantly better survival and lower serum interleukin (IL)-6 and @entity635 levels than their untreated counterparts. In vitro, @entity19 macrophages exposed to LPS and CO had significantly attenuated @entity777 production; this effect was concentration-dependent and occurred at a transcriptional level. The same effect was seen with increased endogenous CO production through overexpression of @entity10183 . Mutation within the @entity9829 -binding site in the @entity777 promoter diminished the effect of CO on promoter activity, and treatment of macrophages with CO decreased @entity9829 binding in an electrophoretic mobility shift assay. Electrophoretic mobility supershift assay indicated that the @entity27619 , @entity42598 , and @entity9830 components of @entity9829 were particularly affected. Upstream of @entity9829 , CO decreased @entity14032 phosphorylation in @entity19 macrophages and lung endothelial cells. @entity19 deficient in the @entity14032 pathway had decreased serum levels of @entity777 and @entity635 in response to LPS compared with control @entity19 , and no effect of CO on these cytokine levels was seen in @entity14032 or @entity18146 genedeleted @entity19 . In summary, these results suggest that CO provides protection in a @entity19 model of @entity295 through modulation of inflammatory cytokine production. For the first time, the effect of CO is shown to be mediated via the @entity14032 signaling pathway and the transcription factor @entity9829 .

Suppression of inflammatory cytokine production by carbon monoxide involves the @entity14032 pathway and XXXX .

@entity27619 :: ('16477(Tax:10090)', 'Gene') :: ['JunB'] @entity295 :: ('MESH:D018805', 'Disease') :: ['sepsis'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse', 'Mice', 'murine'] @entity635 :: ('16176(Tax:10090)', 'Gene') :: ['IL-1beta'] @entity42598 :: ('16478(Tax:10090)', 'Gene') :: ['JunD'] @entity777 :: ('16193(Tax:10090)', 'Gene') :: ['IL-6'] @entity9830 :: ('14281(Tax:10090)', 'Gene') :: ['c-Fos'] @entity14032 :: ('26419(Tax:10090)', 'Gene') :: ['Jnk1', 'JNK'] @entity1850 :: ('MESH:D018746', 'Disease') :: ['sepsis syndrome'] @entity9829 :: ('16476(Tax:10090)', 'Gene') :: ['AP-1'] @entity10183 :: ('15368(Tax:10090)', 'Gene') :: ['heme oxygenase-1'] @entity18146 :: ('26420(Tax:10090)', 'Gene') :: ['Jnk2']
@entity9829 :: (16476(Tax:10090),Gene) :: ['AP-1']
