Abstract
Th17 cells have recently emerged as a major player in inflammatory and autoimmune diseases via the production of pro-inflammatory cytokines IL-17, IL-17F, and IL-22. The differentiation of Th17 cells and the associated cytokine production is directly controlled by RORγt. Here we show that ursolic acid (UA), a small molecule present in herbal medicine, selectively and effectively inhibits the function of RORγt, resulting in greatly decreased IL-17 expression in both developing and differentiated Th17 cells. In addition, treatment with UA ameliorated experimental autoimmune encephalomyelitis. The results thus suggest UA as a valuable drug candidate or leading compound for developing treatments of Th17-mediated inflammatory diseases and cancer.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Infective Agents / pharmacology*
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Cell Differentiation / drug effects
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Cell Differentiation / immunology
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Cell Line
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Encephalomyelitis, Autoimmune, Experimental / drug therapy
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / metabolism
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / immunology
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Humans
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Interleukin-17 / biosynthesis*
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Interleukin-17 / immunology
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Mice
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Neoplasms / drug therapy
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Neoplasms / immunology
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Neoplasms / metabolism
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Nuclear Receptor Subfamily 1, Group F, Member 3 / antagonists & inhibitors*
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Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism*
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Th17 Cells / immunology
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Th17 Cells / metabolism*
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Triterpenes / pharmacology*
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Ursolic Acid
Substances
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Anti-Infective Agents
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IL17F protein, human
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Il17f protein, mouse
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Interleukin-17
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Nuclear Receptor Subfamily 1, Group F, Member 3
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RORC protein, human
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Triterpenes