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Map kinase phosphatase 5 protects against sepsis-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol 2012 May 01;302(9):L866-74

Date

02/07/2012

Pubmed ID

22307906

Pubmed Central ID

PMC3362165

DOI

10.1152/ajplung.00277.2011

Scopus ID

2-s2.0-84860513125   39 Citations

Abstract

Mitogen-activated protein kinases (MAPKs) play a critical role in inflammation. Although activation of MAPK in inflammatory cells has been studied extensively, much less is known about the inactivation of these kinases. MAPK phosphatase 5 (MKP5) is a member of the dual-specificity phosphatase family that dephosphorylates activated MAPKs. Here we report that MKP5 protects sepsis-induced acute lung injury. Mice lacking MKP5 displayed severe lung tissue damage following LPS challenge, characterized with increased neutrophil infiltration and edema compared with wild-type (WT) controls. In response to LPS, MKP5-deficient macrophages produced significantly more inflammatory factors including inflammatory cytokines, nitric oxide, and superoxide. Phosphorylation of p38 MAPK, JNK, and ERK were enhanced in MKP5-deficient macrophages upon LPS stimulation. Adoptive transfer of MKP5-deficient macrophages led to more severe lung inflammation than transfer of WT macrophages, suggesting that MKP5-deficient macrophages directly contribute to acute lung injury. Taken together, these results suggest that MKP5 is crucial to homeostatic regulation of MAPK activation in inflammatory responses.

Author List

Qian F, Deng J, Gantner BN, Flavell RA, Dong C, Christman JW, Ye RD

Author

Benjamin N. Gantner PhD Assistant Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acute Lung Injury
Animals
Bone Marrow Cells
Cells, Cultured
Cytokines
Dual-Specificity Phosphatases
Escherichia coli
Lipopolysaccharides
MAP Kinase Signaling System
Macrophages
Mice
Mice, Knockout
Mitogen-Activated Protein Kinases
Nitric Oxide
Phagocytosis
Phosphorylation
Protein Processing, Post-Translational
Sepsis
Superoxides
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a