MSK
Search
- Page Path
- HOME > Search
Research Support, Non-U.S. Gov't
- A small hairpin RNA targeting myeloid cell leukemia-1 enhances apoptosis in host macrophages infected with Mycobacterium tuberculosis
- Fei-yu Wang , Yu-qing Zhang , Xin-min Wang , Chan Wang , Xiao-fang Wang , Jiang-dong Wu , Fang Wu , Wan-jiang Zhang , Le Zhang
- J. Microbiol. 2016;54(4):330-337. Published online April 1, 2016
- DOI: https://doi.org/10.1007/s12275-016-5627-5
- 55 View
- 0 Download
- 5 Crossref
-
Abstract
- Myeloid cell leukemia-1 (Mcl-1) plays an important role in various cell survival pathways. Some studies indicated that the expression of Mcl-1 was upregulated in host cells during infection with the virulent Mycobacterium tuberculosis strain, H37Rv. The present study was designed to investigate the effect of inhibiting Mcl-1 expression both in vivo and in vitro on apoptosis of host macrophages infected with M. tuberculosis using a small hairpin (sh)RNA. Mcl-1 expression was detected by the real time-polymerase chain reaction, western blotting, and immunohistochemistry. Flow cytometry and transmission electron microscopy were used to measure host macrophage apoptosis. We found elevated Mcl-1 levels in host macrophages infected with M. tuberculosis H37Rv. The expression of Mcl-1 was downregulated efficiently in H37Rv-infected host macrophages using shRNA. Knockdown of Mcl-1 enhanced the extent of apoptosis in H37Rv-infected host macrophages significantly. The increased apoptosis correlated with a decrease in M. tuberculosis colony forming units recovered from H37Rv-infected cells that were treated with Mcl-1-shRNA. Reducing Mcl-1 accumulation by shRNA also reduced accumulation of the anti-apoptotic gene, Bcl-2, and increased expression of the pro-apoptotic gene, Bax, in H37Rv-infected host macrophages. Our results showed that specific knockdown of Mcl-1 expression increased apoptosis of host macrophages significantly and decreased the intracellular survival of a virulent strain of M. tuberculosis. These data indicate that interference with Mcl-1 expression may provide a new avenue for tuberculosis therapy.
-
Citations
Citations to this article as recorded by
- Tolerance of Listeria monocytogenes to biocides used in food processing environments
Sanelisiwe Thinasonke Duze, Musa Marimani, Mrudula Patel
Food Microbiology.2021; 97: 103758. CrossRef - Regulatory role and mechanism of the inhibition of the Mcl-1 pathway during apoptosis and polarization of H37Rv-infected macrophages
Ling Han, Yang Lu, Xiaofang Wang, Shujun Zhang, Yingzi Wang, Fang Wu, Wanjiang Zhang, Xinmin Wang, Le Zhang
Medicine.2020; 99(42): e22438. CrossRef - Current and emerging therapies to combat persistent intracellular pathogens
Philip Arandjelovic, Marcel Doerflinger, Marc Pellegrini
Current Opinion in Pharmacology.2019; 48: 33. CrossRef - PPARĪ³ is critical for Mycobacterium tuberculosis induction of Mcl-1 and limitation of human macrophage apoptosis
Eusondia Arnett, Ashlee M. Weaver, Kiersten C. Woodyard, Maria J. Montoya, Michael Li, Ky V. Hoang, Andrew Hayhurst, Abul K. Azad, Larry S. Schlesinger, Thomas R. Hawn
PLOS Pathogens.2018; 14(6): e1007100. CrossRef - Effect of gap junctions on RAW264.7 macrophages infected with H37Rv
Yang Lu, Xin-min Wang, Pu Yang, Ling Han, Ying-zi Wang, Zhi-hong Zheng, Fang Wu, Wan-jiang Zhang, Le Zhang
Medicine.2018; 97(35): e12125. CrossRef
- Tolerance of Listeria monocytogenes to biocides used in food processing environments
First
Prev
TOP
