AI Article Synopsis
- Sphingosine kinase 1 (SphK1) plays a crucial role in protecting against lung inflammation by suppressing neutrophil oxidant production in response to lipopolysaccharide.
- SphK1's protective effects operate independently of its product, sphingosine 1-phosphate, indicating a distinct pathway for its anti-inflammatory role.
- The mechanism involves SphK1 stabilizing JNK, which prevents the activation of NADPH oxidase and subsequently reduces inflammatory responses and tissue damage.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871452 | PMC |
| http://dx.doi.org/10.1074/jbc.M109.075549 | DOI Listing |
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