Mitogen-activated protein kinase phosphatase 1 as an inflammatory factor and drug target

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Abstract

Mitogen-activated protein kinases (MAPKs) are signaling proteins that are activated through phosphorylation, and they regulate many physiological and pathophysiological processes in cells. Mitogen-activated protein kinase phosphatase 1 (MKP-1) is an inducible nuclear phosphatase that dephosphorylates MAPKs, and thus, it is a negative feedback regulator of MAPK activity. MKP-1 has been found as a key endogenous suppressor of innate immune responses, as well as a regulator of the onset and course of adaptive immune responses. Altered MKP-1 signaling is implicated in chronic inflammatory diseases in man. Interestingly, MKP-1 expression and protein function have been found to be regulated by certain anti-inflammatory drugs, namely by glucocorticoids, antirheumatic gold compounds and PDE4 inhibitors, and MKP-1 has been shown to mediate many of their anti-inflammatory effects. In this Mini Review, we summarize the effect of MKP-1 in the regulation of innate and adaptive immune responses and its role as a potential anti-inflammatory drug target and review recent findings concerning the role of MKP-1 in certain anti-inflammatory drug effects. © 2013 Nordic Pharmacological Society.

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Korhonen, R., & Moilanen, E. (2014, January). Mitogen-activated protein kinase phosphatase 1 as an inflammatory factor and drug target. Basic and Clinical Pharmacology and Toxicology. https://doi.org/10.1111/bcpt.12141

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