Mast cell chymase induces expression of chemokines for neutrophils in eosinophilic EoL-1 cells and mouse peritonitis eosinophils.
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.
Terakawa
Maki
M
Daiichi Asubio Pharma Co. Limited, Biomedical Research Laboratories, 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8513, Japan.
Tomimori
Yoshiaki
Y
Goto
Megumi
M
Fukuda
Yoshiaki
Y
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D053818:Chymases; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009570:Nitriles / Q000494:pharmacology; D010538:Peritonitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D037342:Pertussis Toxin / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000494:pharmacology*
D002070:Butadienes; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D004791:Enzyme Inhibitors; D007093:Imidazoles; D016209:Interleukin-8; D009570:Nitriles; D011725:Pyridines; D011799:Quinazolines; D012333:RNA, Messenger; C466919:SUN-C 8257; C113580:U 0126; D037342:Pertussis Toxin; D020928:Mitogen-Activated Protein Kinases; D012697:Serine Endopeptidases; D053818:Chymases; C093642:SB 203580