MicroRNA-101 targets MAPK phosphatase-1 to regulate the activation of MAPKs in macrophages.
J Immunol
; 185(12): 7435-42, 2010 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-21068409
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
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Fosfatase 1 de Especificidade Dupla
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Imunidade Inata
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Macrófagos
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article