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.
MeSH terms
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Animals
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Anthracenes / pharmacology
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Blotting, Western
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Butadienes / pharmacology
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Butyric Acid / chemistry
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Cell Line, Tumor
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Cell Movement
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Chemotaxis
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Chymases
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Enzyme Inhibitors / pharmacology
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Eosinophils / cytology*
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Eosinophils / metabolism*
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Extracellular Signal-Regulated MAP Kinases / metabolism*
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Humans
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Imidazoles / pharmacology
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JNK Mitogen-Activated Protein Kinases / metabolism
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Mast Cells / enzymology*
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Mice
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Mice, Inbred BALB C
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Mitogen-Activated Protein Kinase 3 / metabolism
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Nitriles / pharmacology
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Pertussis Toxin / pharmacology
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Phosphorylation
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Pyridines / pharmacology
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Receptors, G-Protein-Coupled / metabolism
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Serine Endopeptidases / chemistry*
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Serine Endopeptidases / physiology
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Signal Transduction
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Time Factors
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Anthracenes
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Butadienes
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Enzyme Inhibitors
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Imidazoles
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Nitriles
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Pyridines
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Receptors, G-Protein-Coupled
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U 0126
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Butyric Acid
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pyrazolanthrone
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Pertussis Toxin
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase 3
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p38 Mitogen-Activated Protein Kinases
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Serine Endopeptidases
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Chymases
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SB 203580