Abstract
Synthetic oleanane triterpenoids (CDDO, CDDO-Im and CDDO-Me) are potent anti-inflammatory agents, but have not been investigated for effects on T cell-mediated immune responses. Here we demonstrate that CDDOs have profound immunosuppressive effects on T cell proliferation, development of IL-2 activated LAK cells and cytotoxic T lymphocytes (CTLs), and expression of cytokines at concentrations of 1.25 microM to 0.078 microM. Treatment with CDDO-Me also inhibited the generation of allo-reactive T cell responses in vivo. The suppression of these cell-mediated immune responses by CDDO-Me was associated with the inhibition of NF-kappaB transcription factor.
MeSH terms
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Animals
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Cell Proliferation / drug effects*
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Cells, Cultured
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Cytokines / genetics
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Cytokines / metabolism*
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Cytotoxicity, Immunologic / drug effects*
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Dose-Response Relationship, Drug
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Gene Expression Regulation / drug effects
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I-kappa B Proteins / metabolism
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Imidazoles / pharmacology
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Immunity, Cellular / drug effects*
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Immunosuppressive Agents / pharmacology*
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Isoantigens / immunology
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Killer Cells, Lymphokine-Activated / drug effects
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Killer Cells, Lymphokine-Activated / immunology
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Lymphocyte Activation / drug effects*
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Male
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Mice
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Mice, Inbred C3H
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Mice, Inbred C57BL
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NF-KappaB Inhibitor alpha
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / metabolism
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Oleanolic Acid / analogs & derivatives
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Oleanolic Acid / pharmacology*
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Phosphorylation
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T-Lymphocytes / drug effects*
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T-Lymphocytes / immunology
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T-Lymphocytes, Cytotoxic / drug effects
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T-Lymphocytes, Cytotoxic / immunology
Substances
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1-(2-cyano-3,12-dioxooleana-1,9-dien-28-oyl) imidazole
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Cytokines
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I-kappa B Proteins
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Imidazoles
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Immunosuppressive Agents
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Isoantigens
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NF-kappa B
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Nfkbia protein, mouse
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NF-KappaB Inhibitor alpha
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Oleanolic Acid
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bardoxolone methyl