International journal of clinical and experimental medicine
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Mitogen-activated protein (MAP) kinase cascades are crucial signal transduction pathways in the regulation of the host inflammatory response to infection. MAP kinase phosphatase (MKP)-1, an archetypal member of the MKP family, plays a pivotal role in the deactivation of p38 and JNK. In vitro studies using cultured macrophages have provided compelling evidence for a central role of MKP-1 in the restraint of pro-inflammatory cytokine biosynthesis. ⋯ More recent investigations using intact bacteria confirmed these observations and further revealed novel functions of MKP-1 in host defense against bacterial infection. These studies demonstrate that MKP-1 is an essential feedback regulator of the innate immune response, and that it plays a critical role in preventing septic shock and multi-organ dysfunction during pathogenic infection. In this review, we will summarize the studies on the function of MKP-1 in innate immune responses and discuss the regulation of this novel protein phosphatase.