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Current Molecular Medicine

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ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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Research Article

Verapamil Regulates the Macrophage Immunity to Mycobacterium tuberculosis through NF-κB Signaling

Author(s): Wenping Gong, Ruina Cui, Lele Song, Yourong Yang, Junxian Zhang, Yan Liang, Xuejuan Bai, Jie Wang, Lan Wang, Xueqiong Wu* and Weiguo Zhao*

Volume 23, Issue 6, 2023

Published on: 01 August, 2022

Page: [536 - 549] Pages: 14

DOI: 10.2174/1566524022666220513092244

Price: $65

Abstract

Background: Verapamil enhances the sensitivity of Mycobacterium tuberculosis to anti-tuberculosis (TB) drugs, promotes the macrophage anti-TB ability, and reduces drug resistance, but its mechanism is unclear. Herein, we have investigated the effect of verapamil on cytokine expression in mouse peritoneal macrophages.

Methods: Macrophages from mice infected with M. tuberculosis or S. aureus were cultured with verapamil, the cytokines were detected by enzyme-linked immunosorbent assay, and the RNA was measured with quantitative real-time polymerase chain reaction and agarose gel electrophoresis. The intracellular calcium signaling was measured by confocal microscopy.

Results: Significantly higher levels of NF-κB, IL-12, TNF-α, and IL-1β were observed after TB infection. The levels of NF-κB and IL-12 increased when verapamil concentration was less than 50 μg/ml, but decreased when verapamil concentration was greater than 50μg/ml. With the increase in verapamil concentration, TNF-α and IL-1β expressed by macrophages decreased. The L-type calcium channel transcription significantly increased in M. tuberculosis rather than S. aureus-infected macrophages. Furthermore, during bacillus Calmette-Guerin (BCG) infection, verapamil stimulated a sharp peak in calcium concentration in macrophages, while calcium concentration increased mildly and decreased smoothly over time in the absence of verapamil.

Conclusion: Verapamil enhanced macrophage immunity via the NF-κB pathway, and its effects on cytokine expression may be achieved by its regulation of intracellular calcium signaling.

Keywords: Tuberculosis, verapamil, NF-ΚB, efflux pump, macrophage, intracellular.

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