Downregulation of vimentin in macrophages infected with live Mycobacterium tuberculosis is mediated by Reactive Oxygen Species
| Autor: | R. J. Retnakumar, P. P. Mahesh, Sathish Mundayoor |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Vimentin Apoptosis macromolecular substances Article Cell Line Mycobacterium tuberculosis 03 medical and health sciences 0302 clinical medicine Western blot Downregulation and upregulation Bacterial Proteins medicine Humans Tuberculosis RNA Messenger Antigens Bacterial Multidisciplinary biology medicine.diagnostic_test Macrophages Hydrogen Peroxide biology.organism_classification Molecular biology 030104 developmental biology Gene Expression Regulation Cell culture 030220 oncology & carcinogenesis Immunology biology.protein bacteria Ectopic expression Antibody Reactive Oxygen Species Mycobacterium |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep21526 |
| Popis: | Mycobacterium tuberculosis persists primarily in macrophages after infection and manipulates the host defence pathways in its favour. 2D gel electrophoresis results showed that vimentin, an intermediate filament protein, is downregulated in macrophages infected with live Mycobacterium tuberculosis H37Rv when compared to macrophages infected with heat- killed H37Rv. The downregulation was confirmed by Western blot and quantitative RT-PCR. Besides, the expression of vimentin in avirulent strain, Mycobacterium tuberculosis H37Ra- infected macrophages was similar to the expression in heat-killed H37Rv- infected macrophages. Increased expression of vimentin in H2O2- treated live H37Rv-infected macrophages and decreased expression of vimentin both in NAC and DPI- treated heat-killed H37Rv-infected macrophages showed that vimentin expression is positively regulated by ROS. Ectopic expression of ESAT-6 in macrophages decreased both the level of ROS and the expression of vimentin which implies that Mycobacterium tuberculosis-mediated downregulation of vimentin is at least in part due to the downregulation of ROS by the pathogen. Interestingly, the incubation of macrophages with anti-vimentin antibody increased the ROS production and decreased the survival of H37Rv. In addition, we also showed that the pattern of phosphorylation of vimentin in macrophages by PKA/PKC is different from monocytes, emphasizing a role for vimentin phosphorylation in macrophage differentiation. |
| Databáze: | OpenAIRE |
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