title: Eosinophil migration induced by mast cell chymase is mediated by extracellular signal-regulated kinase pathway.
abstract: Mast cell chymase is known to induce eosinophil migration in vivo and in vitro. In the present study, we investigated possible involvement of mitogen-activated protein (MAP) kinases; extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38, in the chymase-induced eosinophil migration. Human chymase induced a rapid phosphorylation of ERK1/2 and p38 in human eosinophilic leukemia EoL-1 cells, while no phosphorylation was detected in JNK. The chymase-induced phosphorylation of ERK and p38 was inhibited by pertussis toxin. Similar results were obtained in the experiments using mouse chymase and eosinophils. U0126 (the inhibitor for MAP/ERK kinase) suppressed chymase-induced migration of EoL-1 cells and mouse eosinophils. However, SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor) showed little effect on the migration. It is suggested therefore that chymase activates ERK and p38 probably through G-protein-coupled receptor, and that ERK but not p38 cascade may have a crucial role in chymase-induced migration of eosinophils.
authors.affiliation: Daiichi Suntory Biomedical Research Limited, 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8513, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Terakawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tomimori
authors.forename: Megumi
authors.initials: M
authors.lastname: Goto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Shinzo
authors.initials: S
authors.lastname: Oikawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D020148:Butyric Acid / Q000737:chemistry; D045744:Cell Line, Tumor; D002465:Cell Movement; D002633:Chemotaxis; D053818:Chymases; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology* / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008407:Mast Cells / Q000201:enzymology*; D051379:Mice; D008807:Mice, Inbred BALB C; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000502:physiology; D015398:Signal Transduction; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000873:Anthracenes; D002070:Butadienes; D004791:Enzyme Inhibitors; D007093:Imidazoles; D009570:Nitriles; D011725:Pyridines; D043562:Receptors, G-Protein-Coupled; C113580:U 0126; D020148:Butyric Acid; C432165:pyrazolanthrone; D037342:Pertussis Toxin; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D012697:Serine Endopeptidases; D053818:Chymases; C093642:SB 203580