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Verapamil Regulates the Macrophage Immunity to <i>Mycobacterium tuberculosis</i> through NF-&#954;B Signaling

[ Vol. 23 , Issue. 6 ]


Wenping Gong, Ruina Cui, Lele Song, Yourong Yang, Junxian Zhang, Yan Liang, Xuejuan Bai, Jie Wang, Lan Wang, Xueqiong Wu* and Weiguo Zhao*   Pages 536 - 549 ( 14 )


<p>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. <p> 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. <p> Results: Significantly higher levels of NF-&#954;B, IL-12, TNF-&#945;, and IL-1&#946; were observed after TB infection. The levels of NF-&#954;B 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-&#945; and IL-1&#946; 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. <p> Conclusion: Verapamil enhanced macrophage immunity via the NF-&#954;B pathway, and its effects on cytokine expression may be achieved by its regulation of intracellular calcium signaling.</p>


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


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