Regulation of Inflammatory Cytokine Production by MKP‐5 in Macrophages

E-ISSN： 1742-7843|117|2|96-104

ISSN： 1742-7835

Source： BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY (ELECTRONIC), Vol.117, Iss.2, 2015-08, pp. : 96-104

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Abstract

AbstractMitogen‐activated protein kinases (MAPKs) include p38 MAPKs, c‐Jun N‐terminal kinases (JNKs) and Extracellular signal‐regulated kinases (ERKs), and they regulate many cell processes, such as cell division, differentiation and release of inflammatory mediators. MAPK activity is controlled by mitogen‐activated protein kinase phosphatases (MKPs), a phosphatase family with 11 members. MKP‐1 is the most studied member of MKP family, and it is one of the anti‐inflammatory factors induced by glucocorticoids. Less is known about the other MAPK phosphatases although they hold a promise as anti‐inflammatory drug targets. In this study, we investigated the effect of MKP‐5 on MAPK phosphorylation and cytokine production in J774 mouse macrophages. We used MKP‐5 siRNA and an MKP‐5 inhibitor (AS077234‐4) to modulate MKP‐5 function. We found that MKP‐5 controlled p38 MAPK phosphorylation, but not that of JNK or ERK. In addition, the production of IL‐6 and TNF was suppressed by MKP‐5 in macrophages. Our results introduce a novel concept that compounds able to enhance MKP‐5 expression and/or activity hold anti‐inflammatory potential, because MKP‐5 down‐regulates the release of inflammatory mediators by controlling p38 MAPK activity.