维拉帕米
钙
巨噬细胞
肿瘤坏死因子α
结核分枝杆菌
细胞因子
生物学中的钙
化学
药理学
细胞内
微生物学
分子生物学
生物
免疫学
肺结核
医学
生物化学
体外
病理
有机化学
作者
Wenping Gong,Ruina Cui,Lele Song,Yourong Yang,Junxian Zhang,Yan Liang,Xuejuan Bai,Jie Wang,Lan Wang,Xueqiong Wu,Weiguo Zhao
出处
期刊:Current Molecular Medicine
[Bentham Science]
日期:2023-07-01
卷期号:23 (6): 536-549
标识
DOI:10.2174/1566524022666220513092244
摘要
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.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.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.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.
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