Xanthohumol inhibits IL-12 production and reduces chronic allergic contact dermatitis

Xanthohumol inhibits IL-12 production and reduces chronic allergic contact dermatitis
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DOI:
10.1016/j.intimp.2010.02.002
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发表时间:
2010-05-01
影响因子:
5.6
通讯作者:
Kang, Bok Yun
Kang, Bok Yun
中科院分区:
医学2区
文献类型:
--
作者:
Cho, Young-Chang;You, Sung-Kyun;Kang, Bok Yun

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评价了黄腐酚(XN)及其相关化合物调节白细胞介素(IL)-12产生的作用,白细胞介素-12是驱动辅助性T细胞1免疫应答的最重要因素。XN对脂多糖(LPS)或LPS/IFN-γ刺激的巨噬细胞产生IL-12的抑制作用最强。黄腐酚4 '-O-β-D-吡喃葡萄糖苷(XNG)抑制IL-12产生的效果低于XN。异黄腐酚和8-异戊烯基Naringenin对IL-12产生的抑制作用比XNG相对较低。(2S)-5-甲氧基-8-异戊烯基柚皮素7-O-β-D-吡喃葡萄糖苷对IL-12的产生没有任何影响。然后,我们测试了这些化合物如何影响NF-κ B与细胞核中κ B位点的结合活性。这些化合物抑制巨噬细胞中的κ B结合的效力顺序与IL-12抑制相同。此外,我们研究了显示出最有效减少IL-12产生的XN是否减轻了皮肤炎症。慢性过敏性接触性皮炎,银屑病的实验模型,用于确定XN在体内的抗炎作用。XN处理降低了恶唑酮诱导的穗增厚程度。总之,XN可能是有效的抗炎剂,通过抑制IL-12的产生来减少皮肤炎症。(C)2010 Elsevier BV保留所有权利。
Xanthohumol (XN) and its related compounds were evaluated for their effects on modulating the production of interleukin (IL)-12, the most important factor driving T helper 1 immune responses. XN showed the strongest inhibitory effect on IL-12 production in macrophages stimulated by lipopolysaccharide (LPS) or LPS/interferon-gamma. Xanthohumol 4'-O-beta-D-glucopyranoside (XNG) inhibited IL-12 production less effectively than XN. Isoxanthohumol and 8-prenylnaringenin showed comparatively lower inhibitory effects on IL-12 production than XNG. (2S)-5-methoxy-8-prenylnaringenin 7-O-beta-D-glucopyranoside did not exert any effect on IL-12 production. We then tested how these compounds affected NF-kappa B binding activity to the kappa B site in the nucleus. The compounds inhibited kappa B binding in macrophages with the same potency order as IL-12 inhibition. Furthermore, we investigated whether XN, which showed the most effective reduction of IL-12 production, attenuated skin inflammation. Chronic allergic contact dermatitis, an experimental model for psoriasis, was used to determine the anti-inflammatory effects of XN in vivo. XN treatment reduced the degree of ear thickening induced by oxazolone. Taken together, XN might be effective as an anti-inflammatory agent to reduce skin inflammation by inhibiting IL-12 production. (C) 2010 Elsevier B.V. All rights reserved.