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The flavones luteolin and apigenin inhibit in vitro antigen-specific proliferation and interferon-gamma production by murine and human autoimmune T cells

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Author: Verbeek, R. · Plomp, A.C. · Tol, E.A.F. van · Noort, J.M. van
Source:Biochemical Pharmacology, 4, 68, 621-629
Identifier: 237941
doi: doi:10.1016/j.bcp.2004.05.012
Keywords: Apigenin · Autoimmune · EAE · experimental autoimmune encephalomyelitis · Flavonoids · IFN · IL · interferon · interleukin · Luteolin · MS · multiple sclerosis · PLP · proteolipid protein · T cells · crystallin · gamma interferon · morin · proteolipid protein · quercetin · animal cell · antigen specificity · autoimmunity · cell proliferation · cellular immunity · controlled study · cytokine production · drug efficacy · drug inhibition · evaluation · female · human cell · mouse · multiple sclerosis · nonhuman · Animals · Apigenin · Cell Survival · Dose-Response Relationship, Drug · Flavonoids · Humans · Interferon Type II · Luteolin · Lymphokines · Mice · T-Lymphocytes


Plant-derived flavonoids are inhibitors of various intracellular processes, notably phosphorylation pathways, and potential inhibitors of cellular autoimmunity. In this study, the inhibiting effects of various flavonoids on antigen-specific proliferation and interferon-gamma (IFN-γ) production by human and murine autoreactive T cells were evaluated in vitro. T-cell responses were evaluated for the human autoantigen alpha B-crystallin, a candidate autoantigen in multiple sclerosis, and for the murine encephalitogen proteolipid protein peptide PLP (139-151). The flavones apigenin and luteolin were found to be strong inhibitors of both murine and human T-cell responses while fisitin, quercitin, morin and hesperitin, members of the subclasses of flavonoles and flavanones, were ineffective. Antigen-specific IFN-γ production was reduced more effectively by flavones than T-cell proliferation, suggesting that the intracellular pathway for IFN-γ production in T cells is particularly sensitive to flavone inhibition. These results indicate that flavones but not flavanoles or flavanones are effective inhibitors of the potentially pathogenic function of autoreactive T cells. The effects of flavones were the same for human and murine autoreactive T cells, stressing the usefulness of animal models of autoimmunity for further studies on the effects of flavonones on autoimmune diseases. © 2004 Elsevier Inc. All rights reserved. Chemicals / CAS: apigenin, 520-36-5; crystallin, 11046-99-4; gamma interferon, 82115-62-6; hesperetin, 520-33-2; luteolin, 491-70-3; morin, 480-16-0; quercetin, 117-39-5; antigen-specific helper factors; Apigenin, 520-36-5; Flavonoids; Interferon Type II, 82115-62-6; Luteolin, 491-70-3; Lymphokines