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.
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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)
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Chemical References |
- Cytokines
- Lipopolysaccharides
- Superoxides
- Nitric Oxide
- Mitogen-Activated Protein Kinases
- Dusp10 protein, mouse
- Dual-Specificity Phosphatases
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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)
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