u-0126 and Peritonitis

Human chymase induced release of interleukin-8 (IL-8) in human EoL-1 cells that had been differentiated into eosinophil-like cells with butyric acid. The chymase-induced IL-8 production was specific in that other cytokines/chemokines examined were not induced. Human chymase also increased mRNA for IL-8 in the differentiated EoL-1 cells, showing involvement of mRNA synthesis. The chymase-induced IL-8 release was inhibited by pertussis toxin as well as U0126 (an inhibitor for extracellular signal-regulated kinase pathway) and SB203580 (p38 inhibitor), suggesting that the chymase-induced IL-8 production is mediated by G protein-coupled receptor and mitogen-activated protein kinases. Mouse mast cell protease-4 (mMCP-4), a mouse chymase, induced macrophage-inflammatory protein-2 (MIP-2), a mouse homologue for IL-8, in mouse eosinophils in vitro. Intradermal injection of mMCP-4 not only induced skin edema but increased MIP-2 content and neutrophil number at the injection site. Taken together, our findings demonstrate that mast cell chymase may contribute to the interaction between eosinophils and neutrophils by inducing IL-8/MIP-2 in eosinophils at allergic inflamed sites.

Topics: Animals; Butadienes; Cell Line, Tumor; Chemokine CXCL2; Chemokines; Chymases; Cytokines; Dose-Response Relationship, Drug; Enzyme Inhibitors; Eosinophils; Gene Expression; Humans; Imidazoles; Interleukin-8; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; Neutrophils; Nitriles; Peritonitis; Pertussis Toxin; Pyridines; Quinazolines; RNA, Messenger; Serine Endopeptidases