MicroRNA-101 targets MAPK phosphatase-1 to regulate the activation of MAPKs in macrophages.

Qing-Yuan Zhu (1) , Qin Liu (2) , Jian-Xia Chen (1) , Ke Lan (1) , Bao-Xue Ge (1, 2)

1 IPS-CAS - Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences
2 Key Laboratory of Stem Cell Biology

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.

Domains: Immunology

Qing-Yuan Zhu, Qin Liu, Jian-Xia Chen, Ke Lan, Bao-Xue Ge. MicroRNA-101 targets MAPK phosphatase-1 to regulate the activation of MAPKs in macrophages.. Journal of Immunology, 2010, 185 (12), pp.7435-42. ⟨10.4049/jimmunol.1000798⟩. ⟨pasteur-00624971⟩