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.
Verbeek
Richard
R
Division of Biomedical Research, TNO Prevention and Health, P.O. Box 2215, 2301 CE Leiden, The Netherlands.
Plomp
Arianne C
AC
van Tol
Eric A F
EA
van Noort
Johannes M
JM
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