Lihua Liu1, Juanzhi Zhao2, An Li3, Xuan Yang3, Ben Sprangers4, Shengqiao Li3,5. 1. Department of Medical Ultrasonic, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, P.R. China. 2. Department of Pharmacy, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, P.R. China. 3. Department of Traditional Chinese Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, P.R. China. 4. Laboratory of Molecular Immunology, Department of Microbiology and Immunology, Rega Institute, Leuven, Belgium. 5. Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, University of Sun Yat-Sen, Zhuhai, P.R. China.
Abstract
OBJECTIVES: It has been demonstrated that artemisinin (ART) possesses multiple immune modulatory effects. However, its role as immunosuppressant in allogeneic transplantation is undetermined. Here, we investigated the effect of ART on co-stimulatory signaling in OX40+ T cells and evaluated ART as a potential immunosuppressant in transplantation. MATERIALS AND METHODS: Allogeneic skin transplantation was performed in C57BL/6 to BALB/c mice. Recipient mice were administrated with vehicle, ART or cyclosporine A daily from day 0 to day 19 post transplantation. Proportions of splenic CD4+OX40+ and CD4+CD44hiCD62Lhi cells, and serum IgG was measured by using flow cytometry. An in vitro lymphocyte stimulation with Con A or LPS under various concentrations of ART was performed, expression of CD4+OX40+ and CD4+CD44hiCD62Lhi cells was evaluated, and interleukin(IL)-6 production was measured by ELISA. RESULTS: In in vivo allogeneic skin transplant model, ART significantly prolongs allogeneic skin survival. Furthermore, our in vitro studies demonstrate that the immune suppression of ART on T cells is associated with a reduction in OX40+ T cells and inhibition of IL-6 secretion. CONCLUSION: Our data indicate that the OX40-OX40L pathway and IL-6 are possibly involved in ART-induced immunosuppression, and ART is a potential novel immunosuppressant.
OBJECTIVES: It has been demonstrated that artemisinin (ART) possesses multiple immune modulatory effects. However, its role as immunosuppressant in allogeneic transplantation is undetermined. Here, we investigated the effect of ART on co-stimulatory signaling in OX40+ T cells and evaluated ART as a potential immunosuppressant in transplantation. MATERIALS AND METHODS: Allogeneic skin transplantation was performed in C57BL/6 to BALB/c mice. Recipient mice were administrated with vehicle, ART or cyclosporine A daily from day 0 to day 19 post transplantation. Proportions of splenic CD4+OX40+ and CD4+CD44hiCD62Lhi cells, and serum IgG was measured by using flow cytometry. An in vitro lymphocyte stimulation with Con A or LPS under various concentrations of ART was performed, expression of CD4+OX40+ and CD4+CD44hiCD62Lhi cells was evaluated, and interleukin(IL)-6 production was measured by ELISA. RESULTS: In in vivo allogeneic skin transplant model, ART significantly prolongs allogeneic skin survival. Furthermore, our in vitro studies demonstrate that the immune suppression of ART on T cells is associated with a reduction in OX40+ T cells and inhibition of IL-6 secretion. CONCLUSION: Our data indicate that the OX40-OX40L pathway and IL-6 are possibly involved in ART-induced immunosuppression, and ART is a potential novel immunosuppressant.
Entities:
Keywords:
Artemisinin; IL-6; OX40; allogeneic transplantation; memory T cells