The Ca2+ Channel Blocker Verapamil Inhibits the In Vitro Activation and Function of T Lymphocytes: A 2022 Reappraisal

Jose Ignacio Veytia Bucheli; Den Alejandro Alvarado-Velázquez; Lourival Domingos Possani; Roberto González-Amaro; Yvonne Rosenstein

doi:10.3390/pharmaceutics14071478

The Ca²⁺ Channel Blocker Verapamil Inhibits the In Vitro Activation and Function of T Lymphocytes: A 2022 Reappraisal

Jose Ignacio Veytia Bucheli
, Den Alejandro Alvarado-Velázquez
, Lourival Domingos Possani
, Roberto González-Amaro
, Yvonne Rosenstein

Résultats de recherche: Contribution à un journal/une revue › Article › Revue par des pairs

62 Téléchargements (Pure)

Résumé

Ca²⁺ channel blockers (CCBs) are commonly used to treat different cardiovascular conditions. These drugs disrupt the intracellular Ca²⁺ 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.

langue originale	Anglais
Numéro d'article	1478
journal	Pharmaceutics
Volume	14
Numéro de publication	7
Les DOIs	https://doi.org/10.3390/pharmaceutics14071478
Etat de la publication	Publié - juil. 2022

Financement

This research was partially funded by CONACYT (grant number A1-S-15601), and DGAPA/UNAM (grant number IN212519) to Y.R. The APC was funded by Y.R., R.G.-A. and L.D.P. The authors are indebted to Ángel Cárdenas-Hernández for the generous gift of the verapamil hydrochloride used in this work. The authors thank Erika Melchy for technical support, and the members of the Rosenstein and Possani laboratories for their valuable comments on this work. J.I.V.-B. and D.A.A.-V. were recipients of a graduate student fellowship from CONACYT (fellowship holder numbers 289448 and 894574).

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10.3390/pharmaceutics14071478

pharmaceutics-14-01478-v3Version finale publiée, 2,56 MBLicense: CC BY

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@article{b34cb0f4dd5f4dc3b133530db1bf34da,

title = "The Ca2+ Channel Blocker Verapamil Inhibits the In Vitro Activation and Function of T Lymphocytes: A 2022 Reappraisal",

abstract = "Ca2+ channel blockers (CCBs) are commonly used to treat different cardiovascular conditions. These drugs disrupt the intracellular Ca2+ 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.",

keywords = "Ca channel blockers, cytokine production, immunosuppression, T cell activation, verapamil",

author = "\{Veytia Bucheli\}, \{Jose Ignacio\} and Alvarado-Vel{\'a}zquez, \{Den Alejandro\} and Possani, \{Lourival Domingos\} and Roberto Gonz{\'a}lez-Amaro and Yvonne Rosenstein",

note = "Funding Information: This research was partially funded by CONACYT (grant number A1-S-15601), and DGAPA/UNAM (grant number IN212519) to Y.R. The APC was funded by Y.R., R.G.-A. and L.D.P. Funding Information: The authors are indebted to {\'A}ngel C{\'a}rdenas-Hern{\'a}ndez for the generous gift of the verapamil hydrochloride used in this work. The authors thank Erika Melchy for technical support, and the members of the Rosenstein and Possani laboratories for their valuable comments on this work. J.I.V.-B. and D.A.A.-V. were recipients of a graduate student fellowship from CONACYT (fellowship holder numbers 289448 and 894574). Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = jul,

doi = "10.3390/pharmaceutics14071478",

language = "English",

volume = "14",

journal = "Pharmaceutics",

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The Ca²⁺ Channel Blocker Verapamil Inhibits the In Vitro Activation and Function of T Lymphocytes: A 2022 Reappraisal. / Veytia Bucheli, Jose Ignacio; Alvarado-Velázquez, Den Alejandro; Possani, Lourival Domingos et al.
Dans: Pharmaceutics, Vol 14, Numéro 7, 1478, 07.2022.

Résultats de recherche: Contribution à un journal/une revue › Article › Revue par des pairs

TY - JOUR

T1 - The Ca2+ Channel Blocker Verapamil Inhibits the In Vitro Activation and Function of T Lymphocytes

T2 - A 2022 Reappraisal

AU - Veytia Bucheli, Jose Ignacio

AU - Alvarado-Velázquez, Den Alejandro

AU - Possani, Lourival Domingos

AU - González-Amaro, Roberto

AU - Rosenstein, Yvonne

N1 - Funding Information: This research was partially funded by CONACYT (grant number A1-S-15601), and DGAPA/UNAM (grant number IN212519) to Y.R. The APC was funded by Y.R., R.G.-A. and L.D.P. Funding Information: The authors are indebted to Ángel Cárdenas-Hernández for the generous gift of the verapamil hydrochloride used in this work. The authors thank Erika Melchy for technical support, and the members of the Rosenstein and Possani laboratories for their valuable comments on this work. J.I.V.-B. and D.A.A.-V. were recipients of a graduate student fellowship from CONACYT (fellowship holder numbers 289448 and 894574). Publisher Copyright: © 2022 by the authors.

PY - 2022/7

Y1 - 2022/7

N2 - Ca2+ channel blockers (CCBs) are commonly used to treat different cardiovascular conditions. These drugs disrupt the intracellular Ca2+ 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.

AB - Ca2+ channel blockers (CCBs) are commonly used to treat different cardiovascular conditions. These drugs disrupt the intracellular Ca2+ 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.

KW - Ca channel blockers

KW - cytokine production

KW - immunosuppression

KW - T cell activation

KW - verapamil

UR - https://www.scopus.com/pages/publications/85137279064

U2 - 10.3390/pharmaceutics14071478

DO - 10.3390/pharmaceutics14071478

M3 - Article

AN - SCOPUS:85137279064

SN - 1999-4923

VL - 14

JO - Pharmaceutics

JF - Pharmaceutics

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M1 - 1478

ER -