Abstract
Transforming growth factor-beta (TGF-beta) modulates functions of bone marrow-derived cultured mast cells (BMMCs); cell maturation (up-regulation of mouse mast cell proteases (mmcps)), growth arrest and migration. We investigated the roles of p38 MAP kinase and Smad3 in TGF-beta-mediated cell responses in BMMCs. Treating BMMCs with TGF-beta induced the phosphorylation of p38 within 2 h and persisted for 24 h. The involvement of p38 in TGF-beta-induced cell responses depended upon mast cell functions; it was necessary for up-regulation of mmcp-1 and migration, but not for up-regulation of mmcp-7 and inhibition of metabolic activity. New protein synthesis was required for the up-regulation of mmcp-1 but not mmcp-7 in response to TGF-beta treatment, and stabilization of mRNA was partially responsible for the increase in gene transcript of mmcp-1. The decrease in metabolic activity in response to TGF-beta treatment was smaller in Smad3-deficient BMMCs compared to wild-type BMMCs. Maximal migration was detected at a TGF-beta concentration of 40 fM in wild-type BMMCs, whereas TGF-beta-induced migration was absent in Smad3-deficient BMMCs. Thus, the roles of p38 and Smad3 are different among TGF-beta-mediated cell responses in BMMCs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anthracenes / pharmacology
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Blotting, Western
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Bone Marrow Cells / cytology
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / metabolism
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Cells, Cultured
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Chymases / genetics
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Chymases / metabolism
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Flavonoids / pharmacology
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Imidazoles / pharmacology
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Mast Cells / drug effects*
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Mast Cells / metabolism
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Mast Cells / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Inbred Strains
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Mice, Knockout
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Phosphorylation / drug effects
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Pyridines / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Smad3 Protein / deficiency
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Smad3 Protein / genetics
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Smad3 Protein / metabolism*
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Transforming Growth Factor beta / pharmacology*
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Tryptases / genetics
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Tryptases / metabolism
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Up-Regulation / drug effects
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Up-Regulation / genetics
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism*
Substances
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Anthracenes
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Enzyme Inhibitors
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Flavonoids
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Imidazoles
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Pyridines
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RNA, Messenger
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Smad3 Protein
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Transforming Growth Factor beta
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pyrazolanthrone
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p38 Mitogen-Activated Protein Kinases
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Chymases
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Mcpt1 protein, mouse
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Tpsab1 protein, mouse
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Tryptases
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SB 203580
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one