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Regulatory mechanisms of IL-2 and IFNγ suppression by quercetin in T helper cells

Title
Regulatory mechanisms of IL-2 and IFNγ suppression by quercetin in T helper cells
Authors
Yu E.S.Min H.J.An S.Y.Won H.Y.Hong J.H.Hwang E.S.
Ewha Authors
황은숙
SCOPUS Author ID
황은숙scopus
Issue Date
2008
Journal Title
Biochemical Pharmacology
ISSN
0006-2952JCR Link
Citation
vol. 76, no. 1, pp. 70 - 78
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Quercetin is a popular flavonoid compound that is biosynthesized by plants; it is suggested to modulate a variety of inflammatory responses of macrophages and T lymphocytes. Oral administration of quercetin in arthritic rats dramatically diminishes clinical signs of arthritis. Moreover, quercetin ameliorates experimental autoimmune encephalomyelitis, which is associated with Th1-mediated immune responses. Like quercetin inhibits macrophage-induced cytokine production, it also blocks IL-12-dependent JAK-STAT signaling in Th cells. Despite the anti-inflammatory effects of quercetin acting through Th cells, the regulatory mechanisms remain unclear. Here, we studied the function of quercetin in Th cells and found that quercetin suppressed both IFNγ and IL-2 production upon T cell receptor stimulation. Furthermore, we uncovered the regulatory mechanisms of quercetin involved in the inhibition of cytokine production during Th cell activation. The fact that quercetin-derived IFNγ suppression was blocked in T-bet-deficient Th cells demonstrated quercetin act through the modulation of T-bet expression. Whereas IL-2 inhibition by quercetin was independent of T-bet expression, quercetin diminished IL-2Rα expression, which is critical for positive regulatory loop of IL-2 autoactivation. Taken together, quercetin is suggested to repress both IFNγ and IL-2 cytokine production by independent mechanisms; T-bet-dependent IFNγ suppression and IL-2Rα-dependent IL-2 inhibition. © 2008 Elsevier Inc. All rights reserved.
DOI
10.1016/j.bcp.2008.03.020
Appears in Collections:
약학대학 > 약학과 > Journal papers
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