Quercetin, a flavonoid phytoestrogen, ameliorates experimental allergic encephalomyelitis by blocking IL-12 signaling through JAK-STAT pathway in T lymphocyte.
Experimental allergic encephalomyelitis (EAE) is a Th1 cell-mediated inflammatory demyelinating autoimmune disease model of multiple sclerosis (MS). Quercetin (3,3'4',5,7-pentahydroxy flavone) is a flavonoid phytoestrogen that has profound anticancer and anti-inflammatory activities. In this study, we show that in vivo treatment of SJL/J mice with quercetin (i.p. 50 or 100 microg every other day) ameliorates EAE in association with the inhibition of IL-12 production and neural antigen-specific Th1 differentiation. In vitro treatment of activated T cells with quercetin blocks IL-12-induced tyrosine phosphorylation of JAK2, TYK2, STAT3, and STAT4, resulting in a decrease in IL-12-induced T cell proliferation and Th1 differentiation. These findings highlight the fact that quercetin ameliorates EAE by blocking IL-12 signaling and Th1 differentiation and suggest its use in the treatment of MS and other Th1 cell-mediated autoimmune diseases.
Muthian
Gladson
G
Departments of Neurology and Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37212, USA.
Bright
John J
JJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D018664:Interleukin-12 / Q000378:metabolism*; D053614:Janus Kinase 2; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology*; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects*; D013154:Spleen / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D018417:Th1 Cells / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; C494087:Stat3 protein, mouse; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12; D011794:Quercetin; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2