Zhu Zhixiang, Zhao Yunfang, Huo Huixia, Gao Xiaoli, Zheng Jiao, Li Jun, Tu Pengfei
Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China.
Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China.
Eur J Pharmacol. 2016 Nov 15;791:412-423. doi: 10.1016/j.ejphar.2016.09.023. Epub 2016 Sep 15.
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.
过度、持续时间过长或失调的免疫反应会引发免疫紊乱，如炎症性疾病、自身免疫性疾病、过敏性疾病和器官移植排斥反应。在本研究中，我们研究了中国沉香倍半萜衍生物HHX-5对先天性免疫和适应性免疫的抑制作用，以揭示其治疗上述免疫紊乱的潜力。结果表明，HHX-5显著抑制了在先天性免疫中起重要作用的巨噬细胞和中性粒细胞的活化。此外，HHX-5通过抑制初始CD4 T细胞向Th1、Th2和Th17细胞的分化以及抑制CD8 T细胞和B细胞的活化、增殖和分化，强烈抑制适应性免疫。机制研究表明，HHX-5显著抑制巨噬细胞中的STAT1信号通路，并抑制初始CD4 T细胞中的STAT1、STAT4、STAT5和STAT6信号通路。总之，我们证明HHX-5可通过抑制STAT信号通路强烈抑制先天性免疫和适应性免疫，并有潜力开发成为治疗免疫紊乱的治疗药物。
