Abstract
It has been recognized that protease-activated receptors (PARs), interleukin (IL)-4 and IL-6 are involved in the pathogenesis of allergic diseases, and that IL-12 plays a role in adaptive immune response. However, little is known of the effect of IL-12 on protease-induced cytokine release from mast cells. In the present study, we examined potential influence of IL-12 on mast cell PAR expression and IL-4 and IL-6 release. The results showed that IL-12 downregulated the expression of PAR-2 and upregulated expression of PAR-4 on P815 cells. It also downregulated expression of PAR-2 mRNA, and upregulated expression of PAR-1, PAR-3 and PAR-4 mRNAs. However, IL-12 enhanced trypsin- and tryptase-induced PAR-2 and PAR-2 mRNA expression. It was observed that IL-12 induced release of IL-4, but reduced trypsin- and tryptase-stimulated IL-4 secretion from P815 cells. PD98059, U0126 and LY294002 not only abolished IL-12-induced IL-4 release but also inhibited IL-12-induced phosphorylation of extracellular signal-regulated kinase and Akt. In conclusion, IL-12 may serve as a regulator in keeping the balance of Th1 and Th2 cytokine production in allergic inflammation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Butadienes / pharmacology
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Cells, Cultured
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Chromones / pharmacology
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Enzyme Inhibitors / pharmacology
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Flavonoids / pharmacology
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Gene Expression Regulation / drug effects
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Imidazoles / pharmacology
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Interleukin-12 / pharmacology*
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Interleukin-4 / metabolism*
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Mast Cells / drug effects*
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Mast Cells / metabolism*
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Mice
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Morpholines / pharmacology
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Nitriles / pharmacology
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / metabolism
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Pyridines / pharmacology
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RNA, Messenger / metabolism
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Receptors, Proteinase-Activated / genetics
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Receptors, Proteinase-Activated / metabolism*
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Trypsin / pharmacology
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Tryptases / pharmacology
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Tyrphostins / pharmacology
Substances
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Butadienes
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Chromones
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Enzyme Inhibitors
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Flavonoids
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Imidazoles
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Morpholines
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Nitriles
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Pyridines
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RNA, Messenger
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Receptors, Proteinase-Activated
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Tyrphostins
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U 0126
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alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
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Interleukin-12
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Interleukin-4
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Proto-Oncogene Proteins c-akt
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Extracellular Signal-Regulated MAP Kinases
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Trypsin
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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