Dihydrocapsaicin suppresses proinflammatory cytokines expression by enhancing nuclear factor IA in a NF-kappa B-dependent manner
Dihydrocapsaicin suppresses proinflammatory cytokines expression by enhancing nuclear factor IA in a NF-kappa B-dependent manner
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二氢辣椒素通过以 NF-κ B 依赖性方式增强核因子 IA 抑制促炎细胞因子的表达
DOI：
10.1016/j.abb.2016.06.002
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发表时间：
2016
影响因子：
3.9
通讯作者：
Wang Qian
中科院分区：
文献类型：
--
作者：
Zhao Jing-Jing;Hu Yan-Wei;Huang Chuan;Ma Xin;Kang Chun-Min;Zhang Yuan;Guo Feng-Xia;Lu Jing-Bo;Xiu Jian-cheng;Qiu Yu-Rong;Sha Yan-Hua;Gao Ji-Juan;Wang Yan-Chao;Li Pan;Xu Bang-Ming;Zheng Lei;Wang Qian
研究背景动脉粥样硬化是一种慢性炎症性疾病，是世界范围内发病率和死亡率的主要原因。越来越多的证据表明，二氢辣椒素（DHC）具有多种药理和生理作用。然而，DHC对促炎反应的影响和可能的机制在很大程度上仍然不清楚。方法和结果我们发现DHC显著上调THP-1巨噬细胞的NFIA和抑制NF-κB表达。DHC可明显抑制LPS诱导的促炎细胞因子TNF-α、IL-1β和IL-6的上调。我们还观察到，在apoE−/−小鼠中，DHC处理显著增加了NFIA的蛋白水平，同时降低了NF-κB和促炎细胞因子。慢病毒介导的NFIA过表达抑制了apoE−/−小鼠THP-1巨噬细胞和斑块组织中NF-κB和促炎细胞因子的表达。此外，慢病毒介导的NFIA过表达治疗使DHC对NF-κB和促炎细胞因子表达的下调在THP-1巨噬细胞和apoE−/−小鼠中显著加重。此外，治疗与siRNA靶向NF-κB加重抑制促炎细胞因子的慢病毒介导的过表达的NFIA.ConclusionThese观察表明，DHC可以显着降低促炎细胞因子，通过增强NFIA和抑制NF-κB的表达，因此DHC可能是一个有前途的候选人作为一种抗炎药物动脉粥样硬化以及其他疾病。
BackgroundAtherosclerosis is a chronic inflammatory disease and represents the leading cause of morbidity and mortality throughout the world. Accumulating evidences have showed that Dihydrocapsaicin (DHC) has been found to exert multiple pharmacological and physiological effects. Nevertheless, the effects and possible mechanism of DHC on proinflammatory response remain largely unexplained.Methods and resultsWe found that DHC markedly upregulated NFIA and suppressed NF-κB expression in THP-1 macrophages. Up-regulation of proinflammatory cytokines induced by LPS including TNF-α, IL-1β and IL-6 were markedly suppressed by DHC treatment. We also observed that protein level of NFIA was significantly increased while NF-κB and proinflammatory cytokines were decreased by DHC treatment in apoE−/−mice. Lentivirus-mediated overexpression of NFIA suppressed NF-κB and proinflammatory cytokines expression both in THP-1 macrophages and plaque tissues of apoE−/− mice. Moreover, treatment with lentivirus-mediated overexpression of NFIA made the down-regulation of DHC on NF-κB and proinflammatory cytokines expression notably accentuated in THP-1 macrophages and apoE−/−mice. In addition, treatment with siRNA targeting NF-κB accentuated the suppression of proinflammatory cytokines by lentivirus-mediated overexpression of NFIA.ConclusionThese observations demonstrated that DHC can significantly decrease proinflammatory cytokines through enhancing NFIA and inhibiting NF-κB expression and thus DHC may be a promising candidate as an anti-inflammatory drug for atherosclerosis as well as other disorders.