A Novel Function of Sphingosine Kinase 1 Suppression of JNK Activity in Preventing Inflammation and Injury

Anke Di; Takeshi Kawamura; Xiao-Pei Gao; Haiyang Tang; Evgeny Berdyshev; Stephen M. Vogel; You-Yang Zhao; Tiffany Sharma; Kurt Bachmaier; Jingsong Xu; Asrar B. Malik

doi:10.1074/jbc.M109.075549

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A Novel Function of Sphingosine Kinase 1 Suppression of JNK Activity in Preventing Inflammation and Injury

Journal article

Peer reviewed

A Novel Function of Sphingosine Kinase 1 Suppression of JNK Activity in Preventing Inflammation and Injury

Anke Di, Takeshi Kawamura, Xiao-Pei Gao, Haiyang Tang, Evgeny Berdyshev, Stephen M. Vogel, You-Yang Zhao, Tiffany Sharma, Kurt Bachmaier, Jingsong Xu, …

The Journal of biological chemistry, Vol.285(21), pp.15848-15857

05/21/2010

DOI: 10.1074/jbc.M109.075549

PMCID: PMC2871452

PMID: 20299461

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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-κB activation. Therefore, SphK1-mediated down-regulation of JNK activity serves to dampen inflammation and tissue injury.

Lung

Lung Injury

MAP Kinases (MAPKs)

NADPH Oxidase

NF-kappa B

Reactive Oxygen Species (ROS)

Signal Transduction/Protein Kinases/MAP

Details

Title: Subtitle: A Novel Function of Sphingosine Kinase 1 Suppression of JNK Activity in Preventing Inflammation and Injury
Creators: Anke Di - University of Illinois Chicago
Takeshi Kawamura - University of Illinois Chicago
Xiao-Pei Gao - University of Illinois Chicago
Haiyang Tang - University of Illinois Urbana-Champaign
Evgeny Berdyshev - University of Chicago
Stephen M. Vogel - University of Illinois Chicago
You-Yang Zhao - University of Illinois Chicago
Tiffany Sharma - University of Illinois Chicago
Kurt Bachmaier - University of Illinois Chicago
Jingsong Xu - University of Illinois Chicago
Asrar B. Malik - University of Illinois Chicago
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.285(21), pp.15848-15857
DOI: 10.1074/jbc.M109.075549
PMID: 20299461
PMCID: PMC2871452
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: Elsevier Inc
Number of pages: 10
Grant note: P01 HL77806 / National Institutes of Health
Language: English
Date published: 05/21/2010
Academic Unit: Anesthesia
Record Identifier: 9985014846602771

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