Dihydrocapsaicin suppresses proinflammatory cytokines expression by enhancing nuclear factor IA in a NF-κB-dependent manner

• Published in: Archives of biochemistry and biophysics 2016-08, Vol.604, p.27-35
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - chemistry; Apolipoproteins E - genetics; Atherosclerosis - drug therapy; Atherosclerosis - metabolism; Capsaicin - analogs & derivatives; Capsaicin - chemistry; Cytokines - metabolism; DHC; Gene Expression Profiling; Gene Expression Regulation; Humans; Inflammation; Inflammatory cytokines; Interleukin-6 - metabolism; Macrophages - drug effects; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes - cytology; NF-kappa B - metabolism; NF-κB; NFI Transcription Factors - metabolism; NFIA; RNA, Small Interfering - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2016.06.002

Atherosclerosis 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. We 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. These 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. •Effect of DHC on NFIA, NF-κB and inflammatory cytokines expression.•Negative effect of NFIA on NF-κB and inflammatory cytokines expression.•Role of NFIA and NF-κB in DHC-induced proinflammatory response.•DHC may be a promising candidate as an anti-inflammatory drug for atherosclerosis as well as other inflammatory diseases.