Flavonoids such as Luteolin, Fisetin and Apigenin Are Inhibitors of Interleukin-4 and Interleukin-13 Production by ActivatedHuman Basophils

Abstract

Background: We have previously shown that fisetin, a flavonol, inhibits IL-4 and IL-13 synthesis by allergen- or anti-IgE-antibody-stimulated basophils. This time, we investigated the inhibition of IL-4 and IL-13 production by basophils by other flavonoids and attempted to determine the fundamental structure of flavonoids related to inhibition. We additionally investigated whether flavonoids suppress leukotriene C4 synthesis by basophils and IL-4 synthesis by T cells in response to anti-CD3 antibody. Methods: Highly purified peripheral basophils were stimulated for 12 h with anti-IgE antibody alone or anti-IgE antibody plus IL-3 in the presence of various concentrations of 18 different kinds of flavones and flavonols. IL-4 and IL-13 concentrations in the supernatants were then measured. Leukotriene C4 synthesis was also measured after basophils were stimulated for 1 h in the presence of flavonoids. Regarding the inhibitory activity of flavonoids on IL-4 synthesis by T cells, peripheral blood mononuclear cells were cultured with flavonoids in anti-CD3-antibody-bound plates for 2 days. Results: Luteolin, fisetin and apigenin were found to be the strongest inhibitors of both IL-4 and IL-13 production by basophils but did not affect leukotriene C4 synthesis. At higher concentrations, these flavonoids suppressed IL-4 production by T cells. Based on a hierarchy of inhibitory activity, the basic structure for IL-4 inhibition by basophils was determined. Conclusions: Due to the inhibitory activity of flavonoids on IL-4 and IL-13 synthesis, it can be expected that the intake of flavonoids, depending on the quantity and quality, may ameliorate allergic symptoms or prevent the onset of allergic diseases.

Evaluation of Anti-inflammatory and Anti-allergic Effects of Food Components Using DNA Microarray Analysis

“…4) is a flavonoid contained in vegetables and fruits such as onions, strawberries and apples 1 . Fisetin was shown to suppress the degranulation and IL4 and IL13 production in RBL-2H3 rat basophilic cells stimulated by IgE-cross linking 5,6,10 . We first examined the effect of fisetin on IgE/antigen-stimulated degranulation of LAD2 human mast cells.…”

Polyphenols and their Mechanism of Action in Allergic Immune ResponseImmune Response

“…Among all studied polyphenols luteolin, fisetin and apigenin were found to be the strongest inhibitors of both IL-4 [1,19] and IL-13 production by basophils but did not affect leukotriene C4 synthesis [20].…”

“…However, luteolin did inhibit phosphorylation of c-Jun and DNA binding activity of AP-1 in nuclear lysates from stimulated KU812 cells [19]. The flavone luteolin is also a strong inhibitor of human autoimmune T cells [21].…”

Oral Administration of a Hop Water Extract Ameliorates the Development of Dermatitis Induced by the Periodical Topical Application of a Mite Antigen in Atopic Dermatitis Model NC/Nga Mice

“…Such flavonoids as luteolin, fisetin, apigenin, kaempherol, and quercetin have been reported to inhibit IL-4 and IL-13 synthesis by human basophils. 29) Moreover, quercetin and kaempherol-3-O-galactoside have been reported to suppress cysteinyl leukotrien synthesis through the inhibition of phospholipase A 2 and 5-lipoxygenase. 30,31) Quercetin glycosides such as isoquercitrin, rutin and isoquercitrin malonate, and kaempherol glycosides such as astragaline, kaempherol rutinoside and astragaline malonate were contained in HWE.…”