Immunomodulatory activity of synthetic triterpenoids: inhibition of lymphocyte proliferation, cell-mediated cytotoxicity, and cytokine gene expression through suppression of NF-kappaB.
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.
Gao
Xiaohua
X
Division of Surgical Research, Department of Surgery, Henry Ford Health System, Detroit, Michigan, USA.
Deeb
Dorrah
D
Danyluk
Andrew
A
Media
Joseph
J
Liu
Yongbo
Y
Dulchavsky
Scott A
SA
Gautam
Subhash C
SC
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007519:Isoantigens / Q000276:immunology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
C472829:1-(2-cyano-3,12-dioxooleana-1,9-dien-28-oyl) imidazole; D016207:Cytokines; D020672:I-kappa B Proteins; D007093:Imidazoles; D007166:Immunosuppressive Agents; D007519:Isoantigens; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha; D009828:Oleanolic Acid; C445068:bardoxolone methyl