| First Author | Di A | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 21 | Pages | 15848-57 |
| PubMed ID | 20299461 | Mgi Jnum | J:163897 |
| Mgi Id | MGI:4830086 | Doi | 10.1074/jbc.M109.075549 |
| Citation | Di A, et al. (2010) A novel function of sphingosine kinase 1 suppression of JNK activity in preventing inflammation and injury. J Biol Chem 285(21):15848-57 |
| abstractText | 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. |
