Document Detail


MicroRNA-101 targets MAPK phosphatase-1 to regulate the activation of MAPKs in macrophages.
MedLine Citation:
PMID:  21068409     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
MAPK phosphatase-1 (MKP-1) is an archetypical member of the dual-specificity phosphatase family that deactivates MAPKs. Induction of MKP-1 has been implicated in attenuating the LPS- or peptidoglycan-induced biosynthesis of proinflammatory cytokines, but the role of noncoding RNA in the expression of the MKP-1 is still poorly understood. In this study, we show that MKP-1 is a direct target of microRNA-101 (miR-101). Transfection of miR-101 attenuates induction of MKP-1 by LPS as well as prolonged activation of p38 and JNK/stress-activated protein kinase, whereas inhibition of miR-101 enhances the expression of MKP-1 and shortens p38 and JNK activation. We also found that expression of miR-101 is induced by multiple TLR ligands, including LPS, peptidoglycan, or polyinosinic-polycytidylic acid, and that inhibition of PI3K/Akt by LY294002 or Akt RNA interference blocks the induction of miR-101 by LPS in RAW264.7 macrophage cells. Moreover, treatment of cells with dexamethasone, a widely used anti-inflammatory agent, markedly inhibits miR-101 expression and enhances the expression of MKP-1 in LPS-stimulated macrophages. Together, these results indicate that miR-101 regulates the innate immune responses of macrophages to LPS through targeting MKP-1.
Authors:
Qing-Yuan Zhu; Qin Liu; Jian-Xia Chen; Ke Lan; Bao-Xue Ge
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Publication Detail:
Type:  Journal Article     Date:  2010-11-10
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  185     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-03     Completed Date:  2011-01-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7435-42     Citation Subset:  AIM; IM    
Affiliation:
Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents / pharmacology
Cell Line
Dexamethasone / pharmacology
Dual Specificity Phosphatase 1 / biosynthesis,  immunology*
Enzyme Activation / drug effects,  immunology
Gene Expression Regulation, Enzymologic / drug effects
Immunity, Innate / drug effects,  physiology*
Lipopolysaccharides / pharmacology
MAP Kinase Kinase 4 / immunology,  metabolism
Macrophages / immunology*,  metabolism
Mice
MicroRNAs / biosynthesis,  immunology*
Toll-Like Receptors / agonists,  immunology,  metabolism
p38 Mitogen-Activated Protein Kinases / immunology,  metabolism
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Lipopolysaccharides; 0/MicroRNAs; 0/Toll-Like Receptors; 50-02-2/Dexamethasone; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 2.7.12.2/MAP Kinase Kinase 4; EC 3.1.3.48/Dual Specificity Phosphatase 1; EC 3.1.3.48/Dusp1 protein, mouse

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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