| Literature DB >> 20299461 |
Anke Di1, Takeshi Kawamura, Xiao-Pei Gao, Haiyang Tang, Evgeny Berdyshev, Stephen M Vogel, You-Yang Zhao, Tiffany Sharma, Kurt Bachmaier, Jingsong Xu, Asrar B Malik.
Abstract
The mechanism underlying the protective effect of sphingosine kinase 1 (SphK1) in inflammatory injury is not clear. We demonstrated using SphK1-null mice (SphK1(-/-)) the crucial role of SphK1 in suppressing lipopolysaccharide-induced neutrophil oxidant production and sequestration in lungs and mitigating lung inflammatory injury. This effect of SphK1 was independent of the production of sphingosine 1-phosphate, the product of SphK1 activity. The anti-inflammatory effect of SphK1 in the lipopolysaccharide model was mediated through SphK1 interaction with JNK. SphK1 stabilization of JNK in turn inhibited JNK binding to the JNK-interacting protein 3 (JIP3) and thus abrogated the activation of NADPH oxidase and oxidant generation and resultant NF-kappaB activation. Therefore, SphK1-mediated down-regulation of JNK activity serves to dampen inflammation and tissue injury.Entities:
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Year: 2010 PMID： 20299461 PMCID： PMC2871452 DOI： 10.1074/jbc.M109.075549
Source DB: PubMed Journal: J Biol Chem ISSN： 0021-9258 Impact factor: 5.157