Selective Inhibitor of p38 Mitogen-Activated Protein Kinase Inhibits Lipopolysaccharide-Induced Interleukin-8 Expression in

Adult respiratory distress syndrome (ARDS) characterized by permeability edema is observed in severe insults such as bac-teremia sepsis. Interleukin (IL)-8, which chemoattracts and ac-tivates neutrophils, has been suggested to play an important role in the production of ARDS. Therefore, the inhibition of IL-8 production is an important strategy for the treatment of ARDS. Recent studies have revealed the role of p38 mitogen-activated protein (MAP) kinase in cytokine expression and the inhibition by a selective inhibitor of p38 MAP kinase activity of cytokine expression in a variety of cell types. However, little is known about the role of p38 MAP kinase in lipopolysaccharide (LPS)-induced IL-8 expression in pulmonary vascular endothelial cells and the effect of a selective p38 MAP kinase inhibitor on it. In the present study, we therefore attempted to clarify these is-sues. The results showed that LPS induced p38 MAP kinase phosphorylation and activity, and SB 203580 as a selective inhibitor of p38 MAP kinase activity inhibited p38 MAP kinase activity and IL-8 expression in LPS-stimulated pulmonary vas-cular endothelial cells. These results indicate that p38 MAP kinase regulates LPS-induced IL-8 expression in pulmonary vascular endothelial cells. Although it is currently not known whether SB 203580 is capable of producing beneficial effects on ARDS, a strategy of inhibiting p38 MAP kinase activity by a selective p38 MAP kinase inhibitor may apply to the therapy for ARDS. Adult respiratory distress syndrome (ARDS), a form of acute lung injury, which is characterized by permeability edema, is observed in severe insults such as bacteremia sep