7'-(3',4'-dihydroxyphenyl)-N-[(4-methoxyphenyl)ethyl]propenamide (Z23), an effective compound from the Chinese herb medicine Fissistigma oldhamii (Hemsl.) Merr, suppresses T cell-mediated immunity in vitro and in vivo.
Fissistigma oldhamii (Hemsl.) Merr [F. oldhamii], a traditional Chinese herb medicine, is widely used for treating rheumatoid arthritis (RA) in China. Following bioactivity-guided isolation, a representative immunosuppressive compound with low cytotoxicity, 7'-(3',4'-dihydroxyphenyl)-N-[(4-methoxyphenyl)ethyl]propenamide (Z23), was been identified in this herb medicine. We investigated the immunosuppressive effects of Z23 on T cells in vitro and in vivo. The results showed that Z23 in a dose-dependent manner significantly inhibited the proliferation of splenocytes induced by concanavalin A (ConA) and by the mixed lymphocyte culture reaction (MLR), with half inhibitive concentration (IC(50)) values of 6.22 microM and 0.78 microM, respectively. Z23 also dose-dependently inhibited the proliferation and type 1 cytokine (IFN-gamma and IL-2) production of primary T cells stimulated by anti-CD3/CD28 mAbs, but did not affect IL-12 production by mouse peritoneal macrophages (pMphi) stimulated with LPS plus IFN-gamma in vitro. Administration of Z23 (6.25 mg/kg, 12.5 mg/kg, 25 mg/kg, i.p.) dose-dependently suppressed 2,4-dinitrofluorobenzene (DNFB)-induced delayed-type hypersensitivity (DTH) reactions. Furthermore, administration of Z23 (25 mg/kg, i.p.) significantly reduced the incidence and severity of type II bovine collagen (CII)-induced arthritis (CIA), which was associated with the inhibition of CII-specific T cell proliferation and type 1 cytokine (IFN-gamma and IL-2) production. In this study, we report that a representative immunosuppressive compound from F. oldhamii, Z23, effectively inhibits murine immune responses in vitro and in vivo, and that the immunosuppressive effects of Z23 might be attributed to suppression of T cell activation and function and Th1 type cytokine production.
Hu
Xu-Dong
XD
Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China.
Zhong
Xiang-Gen
XG
Zhang
Xiang-Hua
XH
Zhang
Yi-Nan
YN
Zheng
Zong-Ping
ZP
Zhou
Yu
Y
Tang
Wei
W
Yang
Yang
Y
Yang
Yi-Fu
YF
Hu
Li-Hong
LH
Zuo
Jian-Ping
JP
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D029061:Annonaceae / Q000737:chemistry; D015703:Antigens, CD / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy; D002417:Cattle; D024043:Collagen Type II / Q000737:chemistry / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006968:Hypersensitivity, Delayed / Q000188:drug therapy / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D008516:Medicine, Chinese Traditional; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018517:Plant Roots / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
C460621:7'-(3',4'-dihydroxyphenyl)-N-((4-methoxyphenyl)ethyl)propenamide; D000577:Amides; D015703:Antigens, CD; D024043:Collagen Type II; D016207:Cytokines; D007166:Immunosuppressive Agents