A Novel Strategy for TNF-Alpha Production by 2-APB Induced Downregulated SOCE and Upregulated HSP70 in O. tsutsugamushi-Infected Human Macrophages
| Autor: | Siou-Jin Chiu, Hsiu-Wen Li, Tohru Yoshioka, Ching-Ying Wu, Wen-Li Hsu, Ming-Wei Lin, Chia-Jung Yen, Yaw-Bin Huang, Chung-Hsing Chang, Chun-Hsiung Wang, Ming-Hsien Tsai, Jui-Lin Liang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Cell signaling Necrosis Physiology lcsh:Medicine Orienta Tsutsugamushi Signal transduction ERK signaling cascade Pathology and Laboratory Medicine White Blood Cells Mice Intracellular Calcium-Sensing Proteins 0302 clinical medicine Animal Cells Immune Physiology Medicine and Health Sciences lcsh:Science Immune Response Innate Immune System Multidisciplinary Imidazoles Signaling cascades Bacterial Pathogens Orientia tsutsugamushi Intracellular Pathogens Medical Microbiology Cytokines Tumor necrosis factor alpha Cellular Types Pathogens medicine.symptom Research Article Boron Compounds MAPK signaling cascades Immune Cells Immunology Down-Regulation Inflammation Microbiology 03 medical and health sciences Signs and Symptoms Downregulation and upregulation Diagnostic Medicine Heat shock protein medicine Animals Humans HSP70 Heat-Shock Proteins Microbial Pathogens Blood Cells Tumor Necrosis Factor-alpha business.industry Macrophages lcsh:R Biology and Life Sciences Membrane Proteins Cell Biology Molecular Development medicine.disease bacterial infections and mycoses Molecular biology Hsp70 030104 developmental biology Immune System lcsh:Q business Cytokine storm 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | PLoS ONE, Vol 11, Iss 7, p e0159299 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Orientia (O.) tsutsugamushi-induced scrub typhus is endemic across many regions of Asia and the Western Pacific, where an estimated 1 million cases occur each year; the majority of patients infected with O. tsutsugamushi end up with a cytokine storm from a severe inflammatory response. Previous reports have indicated that blocking tumor necrosis factor (TNF)-α reduced cell injury from a cytokine storm. Since TNF-α production is known to be associated with intracellular Ca2+ elevation, we examined the effect of store-operated Ca2+ entry (SOCE) inhibitors on TNF-α production in O. tsutsugamushi-infected macrophages. We found that 2-aminoethoxydiphenyl borate (2-APB), but not SKF96365, facilitates the suppression of Ca2+ mobilization via the interruption of Orai1 expression in O. tsutsugamushi-infected macrophages. Due to the decrease of Ca2+ elevation, the expression of TNF-α and its release from macrophages was repressed by 2-APB. In addition, a novel role of 2-APB was found in macrophages that causes the upregulation of heat shock protein 70 (HSP70) expression associated with ERK activation; upregulated TNF-α production in the case of knockdown HSP70 was inhibited with 2-APB treatment. Furthermore, elevated HSP70 formation unexpectedly did not help the cell survival of O. tsutsugamushi-infected macrophages. In conclusion, the parallelism between downregulated Ca2+ mobilization via SOCE and upregulated HSP70 after treatment with 2-APB against TNF-α production was found to efficiently attenuate an O. tsutsugamushi-induced severe inflammatory response. |
| Databáze: | OpenAIRE |
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