Supannikar Tawinwung1, Nalinrat Petpiroon1, Pithi Chanvorachote2. 1. Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Cell-based Drug and Health Products Development Recearch Unit, Chulalongkorn University, Bangkok, Thailand. 2. Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Cell-based Drug and Health Products Development Recearch Unit, Chulalongkorn University, Bangkok, Thailand pithi_chan@yahoo.com.
Abstract
BACKGROUND/AIM: Novel information on the role of endogenous compounds in regulating physiological and pathological process are of interest, as it may lead to the development of better strategies for disease management. The role of angiotensin II and the signaling of type 1 angiotensin II receptor (AGT1R) in T-lymphocyte activation and interleukin-2 (IL-2) production are largely unknown. MATERIALS AND METHODS: Jurkat T-cells were treated with AGT1R inhibitor candesartan and stimulated with phorbol myristate acetate (PMA) and ionomycin. T-Cell activation, associated cytokine production and levels of signaling proteins were evaluated by flow cytometry and western blot analysis. RESULTS: Candesartan significantly suppressed PMA and ionomycin-induced CD25 expression and IL-2 production. Regarding the molecular mechanism involved, we showed that such suppressive effects of blocking of AGT1R by candesartan resulted in the significant inhibition of ERK activation in PMA-stimulated Jurkat T-cells. The effect of ERK inhibition on T-cell activation was further confirmed. Treatment with FR180204, a specific ERK inhibitor, reduced T-cell activation and IL-2 secretion. CONCLUSION: AGT1R signaling is essential for T-cell activation and IL-2 production, and the inhibition of this pathway suppressed T-cell activation via an ERK-dependent mechanism. Copyright
BACKGROUND/AIM: Novel information on the role of endogenous compounds in regulating physiological and pathological process are of interest, as it may lead to the development of better strategies for disease management. The role of angiotensin II and the signaling of type 1 angiotensin II receptor (AGT1R) in T-lymphocyte activation and interleukin-2 (IL-2) production are largely unknown. MATERIALS AND METHODS: Jurkat T-cells were treated with AGT1R inhibitor candesartan and stimulated with phorbol myristate acetate (PMA) and ionomycin. T-Cell activation, associated cytokine production and levels of signaling proteins were evaluated by flow cytometry and western blot analysis. RESULTS:Candesartan significantly suppressed PMA and ionomycin-induced CD25 expression and IL-2 production. Regarding the molecular mechanism involved, we showed that such suppressive effects of blocking of AGT1R by candesartan resulted in the significant inhibition of ERK activation in PMA-stimulated Jurkat T-cells. The effect of ERK inhibition on T-cell activation was further confirmed. Treatment with FR180204, a specific ERK inhibitor, reduced T-cell activation and IL-2 secretion. CONCLUSION: AGT1R signaling is essential for T-cell activation and IL-2 production, and the inhibition of this pathway suppressed T-cell activation via an ERK-dependent mechanism. Copyright
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