Veytia-Bucheli José Ignacio, Alvarado-Velázquez Den Alejandro, Possani Lourival Domingos, González-Amaro Roberto, Rosenstein Yvonne
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av. Universidad 2001, Cuernavaca 62210, Mexico.
Laboratoire de Chimie Bio-Organique, Département de Chimie, Faculté des Sciences, Université de Namur, Rue de Bruxelles 615, 5000 Namur, Belgium.
Pharmaceutics. 2022 Jul 15;14(7):1478. doi: 10.3390/pharmaceutics14071478.
Ca channel blockers (CCBs) are commonly used to treat different cardiovascular conditions. These drugs disrupt the intracellular Ca signaling network, inhibiting numerous cellular functions in different cells, including T lymphocytes. We explored the effect of the CCB verapamil on normal human peripheral blood T cell activation, proliferation, and cytokine production. Cells were activated by ligating CD3 or CD3/CD28 in the presence or absence of verapamil, and the expression of activation-induced cell surface molecules (CD25, CD40L, CD69, PD-1, and OX40), cell proliferation, and cytokine release were assessed by flow cytometry. Verapamil exerted a dose-dependent inhibitory effect on the expression of all the activation-induced cell surface molecules tested. In addition, verapamil diminished T cell proliferation induced in response to CD3/CD28 stimulation. Likewise, the production of Th1/Th17 and Th2 cytokines was also reduced by verapamil. Our data substantiate a potent in vitro suppressive effect of verapamil on T lymphocytes, a fact that might be relevant in patients receiving CCBs.
钙通道阻滞剂（CCBs）常用于治疗各种心血管疾病。这些药物会破坏细胞内钙信号网络，抑制包括T淋巴细胞在内的不同细胞中的多种细胞功能。我们探究了钙通道阻滞剂维拉帕米对正常人外周血T细胞活化、增殖和细胞因子产生的影响。在有或没有维拉帕米存在的情况下，通过连接CD3或CD3/CD28来激活细胞，并通过流式细胞术评估活化诱导的细胞表面分子（CD25、CD40L、CD69、PD-1和OX40）的表达、细胞增殖和细胞因子释放。维拉帕米对所有测试的活化诱导细胞表面分子的表达均具有剂量依赖性抑制作用。此外，维拉帕米减少了CD3/CD28刺激诱导的T细胞增殖。同样，维拉帕米也降低了Th1/Th17和Th2细胞因子的产生。我们的数据证实了维拉帕米在体外对T淋巴细胞具有强大的抑制作用，这一事实可能与接受CCBs治疗的患者有关。
