Quercetin Inhibits IL-1β-Induced Inflammation, Hyaluronan Production and Adipogenesis in Orbital Fibroblasts from Graves' Orbitopathy

被引:73
作者
Yoon, Jin Sook [1 ]
Lee, Hyun Jung [3 ,4 ]
Choi, Soo Hyun [1 ]
Chang, Eun-Ju [2 ]
Lee, Sang Yeul [1 ]
Lee, Eun Jig [3 ,4 ]
机构
[1] Yonsei Univ, Coll Med, Dept Ophthalmol, Inst Vis Res, Seoul, South Korea
[2] Univ Ulsan, Coll Med, Dept Anat & Cell Biol, Cellular Dysfunct Res Ctr, Seoul, South Korea
[3] Inst Endocrine Res, Brain Korea Project Med Sci 21, Seoul, South Korea
[4] Severance Integrat Res Inst Cerebral & Cardiovasc, Seoul, South Korea
基金
新加坡国家研究基金会;
关键词
THYROID-ASSOCIATED OPHTHALMOPATHY; 3T3-L1; ADIPOCYTES; EYE DISEASE; EXPRESSION; DIFFERENTIATION; PATHOGENESIS; RESVERATROL; MECHANISMS; CELLS; PROLIFERATION;
D O I
10.1371/journal.pone.0026261
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Management of Graves' orbitopathy (GO) is challenging, as no reliable, specific, and safe medical therapeutic agents have yet been developed. We investigated the effect of quercetin in primary cultured orbital fibroblasts from GO, targeting pathways of inflammation, aberrant accumulation of extracellular matrix macromolecules, and adipose tissue expansion. Quercetin significantly attenuated intercellular adhesion molecule-1 (ICAM-1), interleukin (IL) -6, IL-8, and cyclooxygenase (COX) -2 mRNA expression, and inhibited IL-1 beta-induced increases in ICAM-1, IL-6, and IL-8 mRNA. Increased hyaluronan production induced by IL-1 beta or tumor necrosis factor-alpha was suppressed by quercetin in a dose-and time-dependent manner. Treatment with noncytotoxic doses of quercetin inhibited accumulation of intracytoplasmic lipid droplets and resulted in a dose-dependent decrease in expression of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein (C/EBP) alpha, and C/EBP beta proteins. In conclusion, inhibition of inflammation, hyaluronan production, and adipogenesis by the natural plant product quercetin in vitro provides the basis for further study of its potential use in the treatment of GO.
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页数:10
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