title: HHX-5, a derivative of sesquiterpene from Chinese agarwood, suppresses innate and adaptive immunity via inhibiting STAT signaling pathways.
abstract: 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.
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China.
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China.
authors.forename: Huixia
authors.initials: H
authors.lastname: Huo
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Gao
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: drlj666@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: pengfeitu@163.com.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Tu
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D007113:Immunity, Innate / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D000067996:RAW 264.7 Cells; D050791:STAT Transcription Factors / Q000378:metabolism*; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D013154:Spleen / Q000276:immunology; D014934:Wood / Q000737:chemistry*
chemical_list: C000616291:9-hydroxyselina-3, 11-dien-12-al; D016207:Cytokines; D007166:Immunosuppressive Agents; D016328:NF-kappa B; D050791:STAT Transcription Factors; D012717:Sesquiterpenes
keywords: Adaptive immunity; HHX-5; Immunological disorder; Innate immunity; STAT signaling pathways; Sesquiterpene