Mycobacterial HBHA induces endoplasmic reticulum stress-mediatedapoptosis through the generation of reactive oxygen species andcytosolic Ca2+ in murine macrophage RAW 264.7 cells
| Autor: | Jung-Wan Choi, Se Hoon Kim, Yun-Ji Lim, Soo-Na Cho, Hae Jin Kim, Jin Bong Park, J. H. Lee, Park Hs, Kim Ej, Jeong Ja, Chang-Hwa Song |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
mycobacteria Immunology Apoptosis macrophage IκB kinase Biology Cell Line Proinflammatory cytokine Mice Cellular and Molecular Neuroscience Cytosol Lectins medicine Animals ER stress chemistry.chemical_classification Reactive oxygen species Macrophages Endoplasmic reticulum Monocyte Chemotaxis Cell Biology Endoplasmic Reticulum Stress Cell biology medicine.anatomical_structure chemistry Unfolded protein response Original Article Calcium Reactive Oxygen Species |
| Zdroj: | CELL DEATH & DISEASE(4) Cell Death & Disease |
| Popis: | Mycobacterial heparin-binding haemagglutinin antigen (HBHA) is a virulence factor that induces apoptosis of macrophages. Endoplasmic reticulum (ER) stress-mediated apoptosis is an important regulatory response that can be utilised to study the pathogenesis of tuberculosis. In the present study, HBHA stimulation induced ER stress sensor molecules in a caspase-dependent manner. Pre-treatment of RAW 264.7 cells with an IκB kinase 2 inhibitor reduced not only C/EBP homology protein expression but also IL-6 and monocyte chemotactic protein-1 (MCP-1) production. BAPTA-AM reduced both ER stress responses and caspase activation and strongly suppressed HBHA-induced IL-6 and MCP-1 production in RAW 264.7 cells. Enhanced reactive oxygen species (ROS) production and elevated cytosolic [Ca(2+)]i levels were essential for HBHA-induced ER stress responses. Collectively, our data suggest that HBHA induces cytosolic [Ca(2+)]i, which influences the generation of ROS associated with the production of proinflammatory cytokines. These concerted and complex cellular responses induce ER stress-associated apoptosis during HBHA stimulation in macrophages. These results indicate that the ER stress pathway has an important role in the HBHA-induced apoptosis during mycobacterial infection. |
| Databáze: | OpenAIRE |
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