title: Evaluation of the immunosuppressive activity of artesunate in vitro and in vivo.
abstract: Artemisinin and its derivatives have been reported to have immunosuppressive activity in some laboratory studies. However, the detail of mechanism remains to be demonstrated. The objective of this study is to clarify the immunosuppressive activity of artesunate (AST), one kind of artemisinin derivatives, and to find its unexplored mode of action. In vitro, the proliferation of T lymphocytes and its cytotoxicity were measured by WST-1 and MTT assay. In vivo, the immunomodulatory effect of AST was evaluated in a mouse model of delayed type hypersensitivity reaction (DTH), which was based on a T cell-mediated immune response. The data displayed that AST had a relatively high immunosuppressive activity with low toxicity, and could inhibit T lymphocyte proliferation induced by mitogen and alloantigen. Meanwhile, topical administration of AST could suppress DTH response significantly. Moreover, AST could also increase the secretion of TFG-β, coupling with the striking enhance of NF-κB/p65 and Smad2/3 signaling. The promotion of CD4(+)CD25(+) regulatory T cells (Tregs) was shown to be a possible mechanism involved in AST-mediated regulation. Taken together, these observations exhibit the potential of developing AST as a novel safe remedy for the treatment of T cell-mediated immune disorders.
authors.affiliation: Department of Pathogen Biology and Immunology, Logistics University of the Chinese People's Armed Police Force, Tianjin, People's Republic of China. tanli20042001@yahoo.com.cn
authors.forename: Tan
authors.initials: T
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Liu
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Zhang
authors.forename: Huo
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004139:Dinitrofluorobenzene; D004423:Ear / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051899:Smad2 Protein / Q000276:immunology; D051900:Smad3 Protein / Q000276:immunology; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D051996:Transcription Factor RelA / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology
chemical_list: D037621:Artemisinins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007166:Immunosuppressive Agents; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D051996:Transcription Factor RelA; D016212:Transforming Growth Factor beta; D000077332:Artesunate; D004139:Dinitrofluorobenzene