ArticleBMC microbiology2006
M. leprae inhibits apoptosis in THP-1 cells by downregulation of Bad and Bak and upregulation of Mcl-1 gene expression.
Article in BMC microbiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology.Frontiers in immunology · 2018Trial
- MicroRNA biomarkers in leprosy: insights from the Northern Brazilian Amazon population and their implications in disease immune-physiopathology.Frontiers in genetics · 2024Article
- Involvement of AMPKα and MAPK-ERK/-JNK Signals in Docetaxel-Induced Human Tongue Squamous Cell Carcinoma Cell Apoptosis.International journal of molecular sciences · 2022Article
- Quercetin induces tongue squamous cell carcinoma cell apoptosis via the JNK activation-regulated ERK/GSK-3α/β-mediated mitochondria-dependent apoptotic signaling pathway.Oncology letters · 2022Article
- Reduction of host cell mitochondrial activity as Mycobacterium leprae's strategy to evade host innate immunity.Immunological reviews · 2021Review
- The in vitroJournal of inflammation (London, England) · 2019Article
- Gain of function in Mycobacterium bovis BCG Moreau due to loss of a transcriptional repressor.Memorias do Instituto Oswaldo Cruz · 2018Article
- PPARγ is critical for Mycobacterium tuberculosis induction of Mcl-1 and limitation of human macrophage apoptosis.PLoS pathogens · 2018Article
- Mcl-1 signals pathway inhibitors in mouse peritoneal macrophage apoptosis infected with the Xinjiang strain ofInternational journal of clinical and experimental pathology · 2017Article
- IFN-γ fails to overcome inhibition of selected macrophage activation events in response to pathogenic mycobacteria.PloS one · 2017Article
- The regulatory role of Mcl-1 in apoptosis of mouse peritoneal macrophage infected withInternational journal of clinical and experimental pathology · 2017Article
- Genetic Variation in Toll-Interacting Protein Is Associated With Leprosy Susceptibility and Cutaneous Expression of Interleukin 1 Receptor Antagonist.The Journal of infectious diseases · 2016Article
- Article
- Gene expression profiling specifies chemokine, mitochondrial and lipid metabolism signatures in leprosy.PloS one · 2013Article
- Infection of Primary Bovine Macrophages with Mycobacterium avium Subspecies paratuberculosis Suppresses Host Cell Apoptosis.Frontiers in microbiology · 2012Article
- Presence of RD149 deletions in M. tuberculosis Central Asian Strain 1 isolates affect growth and TNFα induction in THP-1 monocytes.PloS one · 2011Article
- PI3K-dependent upregulation of Mcl-1 by human cytomegalovirus is mediated by epidermal growth factor receptor and inhibits apoptosis in short-lived monocytes.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- Regulation of monocytes and macrophages cell fate.Frontiers in bioscience (Landmark edition) · 2009Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVirulent Mycobacterium leprae interfere with host defense mechanisms such as cytokine activation and apoptosis. The mitochondrial pathway of apoptosis is regulated by the Bcl-2 family of proteins. Expression of Fas ligand and apoptotic proteins is found in leprosy lesions and M. leprae has been shown to activate pro-apoptotic Bcl-2 genes, Bak and Bax. However, the mechanism by which M. leprae modulates apoptosis is as yet unclear. We investigated expression of apoptotic genes in THP-1 monocytes in response to infection by M. leprae and non-pathogenic M. bovis BCG.
resultsM. leprae did not induce apoptosis in THP-1 cells, while BCG induced a significant loss of cell viability by 18 h post-infection at both (multiplicity of infection) MOI-10 and 20, with an increase by 48 h. BCG-induced cell death was accompanied by characteristic apoptotic DNA laddering in cells. Non-viable BCG had a limited effect on host cell death suggesting that BCG-induced apoptosis was a function of mycobacterial viability. M. leprae also activated lower levels of TNF-alpha secretion and TNF-alpha mRNA expression than BCG. Mycobacterium-induced activation of apoptotic gene expression was determined over a time course of infection. M. leprae reduced Bad and Bak mRNA expression by 18 h post-stimulation, with a further decrease at 48 h. Outcome of cell viability is determined by the ratio between pro- and anti-apoptotic proteins present in the cell. M. leprae infection resulted in downregulation of gene expression ratios, Bad/Bcl-2 mRNA by 39% and Bak/Bcl-2 mRNA by 23%. In contrast, live BCG increased Bad/Bcl-2 mRNA (29 %) but had a negligible effect on Bak/Bcl-2 mRNA. Heat killed BCG induced only a negligible (1-4 %) change in mRNA expression of either Bak/Bcl-2 or Bad/Bcl-2. Additionally, M. leprae upregulated the expression of anti-apoptotic gene Mcl-1 while, BCG downregulated Mcl-1 mRNA.
conclusionThis study proposes an association between mycobacterium-induced apoptosis in THP-1 cells and the regulation of Bcl-2 family of proteins. M. leprae restricts apoptosis in THP-1 cells by downregulation of Bad and Bak and upregulation of Mcl-1 mRNA expression.
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