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Suppressive effect of a novel water-soluble artemisinin derivative SM905 on T cell activation and proliferation in vitro and in vivo.
Eur J Pharmacol. 2007 Jun 14; 564(1-3):211-8.EJ

Abstract

Artemisinin and its derivatives exhibit potent immunosuppressive activity. The aim of this study was to investigate the suppressive effects of SM905, a new water-soluble artemisinin derivative, on T lymphocytes both in vitro and in vivo, and explore its potential mode of action. The results showed that SM905 had a high inhibitory activity in Concanavalin A (ConA)-induced splenocyte proliferation and mixed lymphocyte reaction, and a relatively low cytotoxicity in vitro. In ovalbumin-immunized mice, oral administration of SM905 dose-dependently suppressed T cell proliferative response to ovalbumin, and inhibited anti-ovalbumin interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production by T cells. Further studies showed that SM905 inhibited TCR (T cell receptor)/CD3 plus CD28-mediated primary T cell proliferation and cytokine production (IL-2 and IFN-gamma), and exerted an inhibitory action on the phosphorylation of mitogen-activated protein (MAP) kinases including extracellular signal-regulated kinase (ERK), p38 and Jun N-terminal kinase (JNK), and the activation of Ras. The results of this study provided experimental evidence that the new artemisinin derivative SM905 had immunosuppressive effects both in vitro and in vivo. SM905 suppressed T cell activation, which was associated with the inhibition of MAP kinases and Ras activation. Our results suggested a potential of SM905 to be developed as a new type agent for treating T cell-mediated immune disorder.

Authors+Show Affiliations

First Department of Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17349993

Citation

Wang, Jun-Xia, et al. "Suppressive Effect of a Novel Water-soluble Artemisinin Derivative SM905 On T Cell Activation and Proliferation in Vitro and in Vivo." European Journal of Pharmacology, vol. 564, no. 1-3, 2007, pp. 211-8.
Wang JX, Tang W, Yang ZS, et al. Suppressive effect of a novel water-soluble artemisinin derivative SM905 on T cell activation and proliferation in vitro and in vivo. Eur J Pharmacol. 2007;564(1-3):211-8.
Wang, J. X., Tang, W., Yang, Z. S., Wan, J., Shi, L. P., Zhang, Y., Zhou, R., Ni, J., Hou, L. F., Zhou, Y., He, P. L., Yang, Y. F., Li, Y., & Zuo, J. P. (2007). Suppressive effect of a novel water-soluble artemisinin derivative SM905 on T cell activation and proliferation in vitro and in vivo. European Journal of Pharmacology, 564(1-3), 211-8.
Wang JX, et al. Suppressive Effect of a Novel Water-soluble Artemisinin Derivative SM905 On T Cell Activation and Proliferation in Vitro and in Vivo. Eur J Pharmacol. 2007 Jun 14;564(1-3):211-8. PubMed PMID: 17349993.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suppressive effect of a novel water-soluble artemisinin derivative SM905 on T cell activation and proliferation in vitro and in vivo. AU - Wang,Jun-Xia, AU - Tang,Wei, AU - Yang,Zhong-Shun, AU - Wan,Jin, AU - Shi,Li-Ping, AU - Zhang,Yu, AU - Zhou,Ru, AU - Ni,Jia, AU - Hou,Li-Fei, AU - Zhou,Yu, AU - He,Pei-Lan, AU - Yang,Yi-Fu, AU - Li,Ying, AU - Zuo,Jian-Ping, Y1 - 2007/02/16/ PY - 2006/10/31/received PY - 2007/01/29/revised PY - 2007/01/31/accepted PY - 2007/3/14/pubmed PY - 2007/8/19/medline PY - 2007/3/14/entrez SP - 211 EP - 8 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 564 IS - 1-3 N2 - Artemisinin and its derivatives exhibit potent immunosuppressive activity. The aim of this study was to investigate the suppressive effects of SM905, a new water-soluble artemisinin derivative, on T lymphocytes both in vitro and in vivo, and explore its potential mode of action. The results showed that SM905 had a high inhibitory activity in Concanavalin A (ConA)-induced splenocyte proliferation and mixed lymphocyte reaction, and a relatively low cytotoxicity in vitro. In ovalbumin-immunized mice, oral administration of SM905 dose-dependently suppressed T cell proliferative response to ovalbumin, and inhibited anti-ovalbumin interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production by T cells. Further studies showed that SM905 inhibited TCR (T cell receptor)/CD3 plus CD28-mediated primary T cell proliferation and cytokine production (IL-2 and IFN-gamma), and exerted an inhibitory action on the phosphorylation of mitogen-activated protein (MAP) kinases including extracellular signal-regulated kinase (ERK), p38 and Jun N-terminal kinase (JNK), and the activation of Ras. The results of this study provided experimental evidence that the new artemisinin derivative SM905 had immunosuppressive effects both in vitro and in vivo. SM905 suppressed T cell activation, which was associated with the inhibition of MAP kinases and Ras activation. Our results suggested a potential of SM905 to be developed as a new type agent for treating T cell-mediated immune disorder. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17349993/Suppressive_effect_of_a_novel_water_soluble_artemisinin_derivative_SM905_on_T_cell_activation_and_proliferation_in_vitro_and_in_vivo_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)00184-7 DB - PRIME DP - Unbound Medicine ER -