Mitogen-Activated Protein Kinase Phosphatase-1 Negatively Regulates the Expression of Interleukin-6, Interleukin-8, and

Mitogen-activated protein kinase phosphatase (MKP)-1 is a protein phosphatase that regulates the activity of p38 mitogen-activated protein (MAP) kinase and c-Jun NH2-terminal kinase (JNK) and, to lesser extent, p42/44 extracellular signal-regu-lated kinase. Studies with MKP-1(/) mice show that MKP-1 is a regulating factor suppressing excessive cytokine produc-tion and inflammatory response. The data on the role of MKP-1 in the regulation of inflammatory gene expression in human cells are much more limited. In the present study, we investigated the effect of MKP-1 on the expression of interleukin (IL)-6, IL-8 and cyclooxygenase (COX)-2 in response to stimulation with cytokines (tumor necrosis factor, IL-1, and interferon-; 10 ng/ml each) in A549 human lung epithelial cells. Cytokines enhanced p38 and JNK phosphorylation and MKP-1 expression. p38 MAP kinas