Investigation of the immunosuppressive activity of artemether on T-cell activation and proliferation

BACKGROUND AND PURPOSE: Artemisinin and its derivatives exhibit potent immunosuppressive activity. The purpose of the current study was to examine the immunosuppressive activity of artemether directly on T lymphocytes and to explore its potential mode of action. EXPERIMENTAL APPROACH: In vitro, T-cell proliferation was measured using [(3)H]-thymidine incorporation assay in cells stimulated with ConA, alloantigen and anti-CD3 antibody. CFSE-labeled cell division and cell cycle distribution were monitored by flow cytometry. In vivo, the effects of artemether were evaluated in delayed-type hypersensitivity (DTH) and purified T-cell responses to ovalbumin in ovalbumin-immunized mice. The activation of extracellular signal-regulated kinase1/2 (ERK1/2) and Raf1 were assessed by Western blot analysis and the activation of Ras was tested in pull-down assays. KEY RESULTS: We show that, in vitro, artemether suppressed ConA- or alloantigen-induced splenocyte proliferation, influenced production of the cytokines IL-2 and IFN-gamma and inhibited cell cycle progression through the G0/G1 transition. In vivo, administration of artemether attenuated CD4 T-cell-mediated DTH reaction, and suppressed antigen-specific T-cell response in immunized mice. Further experiments showed that, treatment with artemether impaired both antigen- and anti-CD3-induced phosphorylation of ERK. In primary T cells, artemether profoundly inhibited anti-CD3-induced phosphorylation of Raf1 and activation of Ras. CONCLUSIONS AND IMPLICATIONS: This study provided experimental evidence of the immunosuppressive effects of artemether directly on T cells both in vitro and in vivo. Its immunosuppressive mechanism involved inhibition of the activation of the Ras-Raf1-ERK1/2 protein kinase cascade in T cells.

Wang, J.-X.
Tang, W.
Shi, L.-P.
Wan, J.
Zhou, R.
Ni, J.
Fu, Y.-F.
Yang, Y.-F.
Li, Y.
Zuo, J.-P.
Item Type: 
Journal Article
Publication Title: 
British Journal of Pharmacology
Journal Abbreviation: 
Br. J. Pharmacol.
Publication Date: 
Publication Year: 
Library Catalog: 
PMID: 17262016 PMCID: PMC2189761

Turabian/Chicago Citation

J.-X. Wang, W. Tang, L.-P. Shi, J. Wan, R. Zhou, J. Ni, Y.-F. Fu, Y.-F. Yang, Y. Li and J.-P. Zuo. 3/7/2015. "Investigation of the immunosuppressive activity of artemether on T-cell activation and proliferation." British Journal of Pharmacology 150: 5: 652-661. 10.1038/sj.bjp.0707137.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1038/sj.bjp.0707137 | issn = 0007-1188 | volume = 150 | pages = 652-661 | last = Wang | first = J.-X. | coauthors = Tang, W., Shi, L.-P., Wan, J., Zhou, R., Ni, J., Fu, Y.-F., Yang, Y.-F., Li, Y., Zuo, J.-P. | title = Investigation of the immunosuppressive activity of artemether on T-cell activation and proliferation | journal = British Journal of Pharmacology | date = 3/7/2015 | pmid = | pmc = }} </ref>