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

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.