HHX-5, a derivative of sesquiterpene from Chinese agarwood, suppresses innate and adaptive immunity via inhibiting STAT signaling pathways

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• 作者：Zhixiang Zhu¹ ; Yunfang Zhao¹ ; Huixia Huo ; Xiaoli Gao ; Jiao Zheng ; Jun Li ; ^{drlj666@163.com" class="auth_mail" title="E-mail the corresponding author} ; Pengfei Tu ; ^{pengfeitu@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Immunological disorder ; HHX-5 ; Sesquiterpene ; Innate immunity ; Adaptive immunity ; STAT signaling pathways
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 November 2016
• 年：2016
• 卷：791
• 期：Complete
• 页码：412-423
• 全文大小：6388 K

文摘

Induction of excessive, prolonged, or dysregulated immune responses causes immunological disorders, such as inflammatory diseases, autoimmune diseases, allergic diseases, and organ-graft rejections. In the present study, we investigated the inhibitory effects of HHX-5, a derivative of sesquiterpene from Chinese agarwood, on innate and adaptive immunity for revealing its potential to treat above immunological disorders. The results showed that HHX-5 significantly inhibited the activation of macrophages and neutrophils which play important roles in innate immunity. Furthermore, HHX-5 strongly suppressed adaptive immunity via inhibiting differentiation of naive CD4⁺ T cells into Th1, Th2, and Th17 cells and suppressing activation, proliferation and differentiation of CD8⁺ T cells and B cells. The mechanism study showed that HHX-5 significantly inhibited STAT1 signaling pathway in macrophages and suppressed STAT1, STAT4, STAT5, and STAT6 signaling pathways in naive CD4⁺ T cells. In conclusion, we demonstrated that HHX-5 can strongly inhibit innate and adaptive immunity via suppressing STAT signaling pathways and has potential to be developed into therapeutic drug for treat immunological disorders.