The flavones luteolin and apigenin inhibit in vitro antigen-specific proliferation and interferon-gamma production by murine and human autoimmune T cells.
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-gamma) 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-gamma production was reduced more effectively by flavones than T-cell proliferation, suggesting that the intracellular pathway for IFN-gamma 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.
Division of Biomedical Research, TNO Prevention and Health, P.O. Box 2215, 2301 CE Leiden, The Netherlands.
Richard
R
Verbeek
Arianne C
AC
Plomp
Eric A F
EA
van Tol
Johannes M
JM
van Noort
D000818:Animals; D047310:Apigenin; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D047311:Luteolin; D008222:Lymphokines / Q000502:physiology; D051379:Mice; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D005419:Flavonoids; D008222:Lymphokines; C057264:antigen-specific helper factors; D047310:Apigenin; D007371:Interferon-gamma; D047311:Luteolin