title: Obaculactone exerts a novel ameliorating effect on contact dermatitis through regulating T lymphocyte.
abstract: It is still deficient that an immunosuppressant with a negligible toxicity for patients suffering from contact hypersensitivity. In the present study, we identified a natural occurring compound named obaculactone that effectively alleviated the macroscopic and microscopic appearances of the contact hypersensitivity, while it scarcely possessed toxic effect on mice at 5-20mg/kg. The mRNAs of IL-2, IL-17a, TNF-α and IFN-γ expressed in lymph nodes of mice with dermatitis were also decreased by obaculactone in a dose-dependent manner. Moreover, the hypersensitivity couldn't be adoptively transferred from obaculactone-treated donor mice to normal mice. In vitro study, proliferation arrest in activated hapten-specific T cells and anti-CD3/CD28 stimulated T cells were observed in obaculactone-treated groups. In addition, the enhanced expressions of CD25 and CD69 in activated T cells were reduced by obaculactone. Meanwhile, obaculactone caused G0/G1 phase arrest and up-regulated the levels of cleaved-caspases and cleaved-PARP inducing apoptosis in activated T cells. Taken together, suppressing cell growth in activated T lymphocytes may contribute to the novel ameliorating effect for obaculactone against the contact hypersensitivity.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Xingqi
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: He
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Zijun
authors.initials: Z
authors.lastname: Ouyang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. Electronic address: wuxf@nju.edu.cn.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. Electronic address: molpharm@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects; D018106:CD28 Antigens; D017252:CD3 Complex / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003877:Dermatitis, Contact / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D037181:Lectins, C-Type / Q000096:biosynthesis; D036701:Limonins / Q000627:therapeutic use*; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D020169:Caspases; D016207:Cytokines; D037181:Lectins, C-Type; D036701:Limonins; D012333:RNA, Messenger; D000099192:CD69 Antigens; C001546:limonin
keywords: Allergic contact dermatitis; Apoptosis; Cell cycle; Obaculactone; T lymphocyte