Map kinase phosphatase 5 protects against sepsis-induced acute lung injury.

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.

• Authors: Feng Qian, Jing Deng, Benjamin N Gantner, Richard A Flavell, Chen Dong, John W Christman, Richard D Ye
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 302 Issue 9 Pg. L866-74 (May 01 2012) ISSN: 1522-1504 [Electronic] United States
• PMID: 22307906 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cytokines
• Lipopolysaccharides
• Superoxides
• Nitric Oxide
• Mitogen-Activated Protein Kinases
• Dusp10 protein, mouse
• Dual-Specificity Phosphatases

Topics

• Acute Lung Injury (enzymology, etiology, immunology)
• Animals
• Bone Marrow Cells (immunology, metabolism)
• Cells, Cultured
• Cytokines (biosynthesis)
• Dual-Specificity Phosphatases (deficiency, genetics, physiology)
• Escherichia coli
• Lipopolysaccharides (pharmacology)
• MAP Kinase Signaling System
• Macrophages (immunology, metabolism, physiology)
• Mice
• Mice, Knockout
• Mitogen-Activated Protein Kinases (metabolism)
• Nitric Oxide (biosynthesis)
• Phagocytosis
• Phosphorylation
• Protein Processing, Post-Translational
• Sepsis (complications, immunology)
• Superoxides (metabolism)