Abstract
Involvement of p38 mitogen-activated protein (MAP) kinase in human T cell cytokine synthesis was investigated. p38 MAP kinase was clearly induced in human Th cells activated through the TCR. SB203580, a highly selective inhibitor of p38 MAP kinase, inhibited the induction of p38 MAP kinase in human Th cells. Major T cell cytokines, IL-2, IL-4, IL-5, and IFN-gamma, were produced by Der f 2-specific Th clones upon stimulation through the TCR. IL-5 synthesis alone was significantly inhibited by SB203580 in a dose-dependent manner, whereas the production of IL-2, IL-4, and IFN-gamma was not affected. The proliferation of activated T cells was not affected. IL-5 synthesis of human Th clones induced upon stimulation with rIL-2, phorbol ester plus anti-CD28 mAb, and immobilized anti-CD3 mAb plus soluble anti-CD28 mAb was also suppressed by SB203580 in the same concentration response relationship. The results clearly indicated that IL-5 synthesis by human Th cells is dependent on p38 MAP kinase activity, and is regulated distinctly from IL-2, IL-4, and IFN-gamma synthesis. Selective control of IL-5 synthesis will provide a novel treatment devoid of generalized immune suppression for bronchial asthma and atopic dermatitis that are characterized by eosinophilic inflammation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Clone Cells / drug effects
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Clone Cells / enzymology
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Clone Cells / immunology
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Enzyme Activation / immunology
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Enzyme Inhibitors / pharmacology
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Growth Inhibitors / pharmacology
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Humans
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Imidazoles / pharmacology
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Immunosuppressive Agents / pharmacology
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Interferon-gamma / antagonists & inhibitors
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Interferon-gamma / biosynthesis
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Interleukin-2 / antagonists & inhibitors
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Interleukin-2 / biosynthesis
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Interleukin-4 / antagonists & inhibitors
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Interleukin-4 / biosynthesis
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Interleukin-5 / antagonists & inhibitors
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Interleukin-5 / biosynthesis*
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Interleukin-5 / genetics
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Intracellular Signaling Peptides and Proteins
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / physiology*
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Muromonab-CD3 / pharmacology
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Protein Serine-Threonine Kinases / metabolism
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Pyridines / pharmacology
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RNA, Messenger / antagonists & inhibitors
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RNA, Messenger / biosynthesis
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T-Lymphocytes / cytology
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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T-Lymphocytes, Helper-Inducer / drug effects
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T-Lymphocytes, Helper-Inducer / enzymology
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T-Lymphocytes, Helper-Inducer / metabolism
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p38 Mitogen-Activated Protein Kinases
Substances
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Enzyme Inhibitors
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Growth Inhibitors
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Imidazoles
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Immunosuppressive Agents
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Interleukin-2
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Interleukin-5
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Intracellular Signaling Peptides and Proteins
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Muromonab-CD3
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Pyridines
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RNA, Messenger
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Interleukin-4
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Interferon-gamma
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MAP-kinase-activated kinase 2
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Protein Serine-Threonine Kinases
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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SB 203580