Title:Verapamil Regulates the Macrophage Immunity to Mycobacterium
tuberculosis through NF-κB Signaling
Volume: 23
Issue: 6
Author(s): Wenping Gong, Ruina Cui, Lele Song, Yourong Yang, Junxian Zhang, Yan Liang, Xuejuan Bai, Jie Wang, Lan Wang, Xueqiong Wu*Weiguo Zhao*
Affiliation:
- Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of
Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The 8th Medical Center of PLA
General Hospital, 17 Heishanhu Road, Haidian District, Beijing 100091, China
- Senior Department of
Respiratory and Critical Care Medicine, The 8th Medical Center of PLA General Hospital, 17 Heishanhu
Road, Haidian District, Beijing 100091, China
Keywords:
Tuberculosis, verapamil, NF-ΚB, efflux pump, macrophage, intracellular.
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.
