Regulatory mechanisms of IL-2 and IFNgamma suppression by quercetin in T helper cells.
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 IFNgamma 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 IFNgamma 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-2R alpha expression, which is critical for positive regulatory loop of IL-2 autoactivation. Taken together, quercetin is suggested to repress both IFNgamma and IL-2 cytokine production by independent mechanisms; T-bet-dependent IFNgamma suppression and IL-2R alpha-dependent IL-2 inhibition.
Yu
Eun Sun
ES
College of Pharmacy and Division of Life and Pharmaceutical Sciences and Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul 120-750, Republic of Korea.
Min
Hyun Jung
HJ
An
Su Yeon
SY
Won
Hee Yeon
HY
Hong
Jeong Ho
JH
Hwang
Eun Sook
ES
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D011794:Quercetin / Q000494:pharmacology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology; D014158:Transcription, Genetic
D016207:Cytokines; D007376:Interleukin-2; D007371:Interferon-gamma; D011794:Quercetin