Repetitive Low-Level Blast Exposure via Akt/NF-κB Signaling Pathway Mediates the M1 Polarization of Mouse Alveolar Macrophage MH-S Cells
Repetitive low-level blast (rLLB) exposure is a potential risk factor for the health of soldiers or workers who are exposed to it as an occupational characteristic. Alveolar macrophages (AMs) are susceptible to external blast waves and produce pro-inflammatory or anti-inflammatory effects. However,...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/13/10596 |
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| author | Chenhao Geng Xinyue Wang Jiale Chen Na Sun Yuru Wang Zizheng Li Lu Han Shike Hou Haojun Fan Ning Li Yanhua Gong |
| author_facet | Chenhao Geng Xinyue Wang Jiale Chen Na Sun Yuru Wang Zizheng Li Lu Han Shike Hou Haojun Fan Ning Li Yanhua Gong |
| author_sort | Chenhao Geng |
| collection | DOAJ |
| description | Repetitive low-level blast (rLLB) exposure is a potential risk factor for the health of soldiers or workers who are exposed to it as an occupational characteristic. Alveolar macrophages (AMs) are susceptible to external blast waves and produce pro-inflammatory or anti-inflammatory effects. However, the effect of rLLB exposure on AMs is still unclear. Here, we generated rLLB waves through a miniature manual Reddy-tube and explored their effects on MH-S cell morphology, phenotype transformation, oxidative stress status, and apoptosis by immunofluorescence, real-time quantitative PCR (qPCR), western blotting (WB) and flow cytometry. Ipatasertib (GDC-0068) or PDTC was used to verify the role of the Akt/NF-κB signaling pathway in these processes. Results showed that rLLB treatment could cause morphological irregularities and cytoskeletal disorders in MH-S cells and promote their polarization to the M1 phenotype by increasing iNOS, CD86 and IL-6 expression. The molecular mechanism is through the Akt/NF-κB signaling pathway. Moreover, we found reactive oxygen species (ROS) burst, Ca<sup>2+</sup> accumulation, mitochondrial membrane potential reduction, and early apoptosis of MH-S cells. Taken together, our findings suggest rLLB exposure may cause M1 polarization and early apoptosis of AMs. Fortunately, it is blocked by specific inhibitors GDC-0068 or PDTC. This study provides a new treatment strategy for preventing and alleviating health damage in the occupational population caused by rLLB exposure. |
| first_indexed | 2024-03-11T01:40:20Z |
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| id | doaj.art-ba17fe349b9e409d9e790ca9b8c76eb9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:40:20Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ba17fe349b9e409d9e790ca9b8c76eb92023-11-18T16:40:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131059610.3390/ijms241310596Repetitive Low-Level Blast Exposure via Akt/NF-κB Signaling Pathway Mediates the M1 Polarization of Mouse Alveolar Macrophage MH-S CellsChenhao Geng0Xinyue Wang1Jiale Chen2Na Sun3Yuru Wang4Zizheng Li5Lu Han6Shike Hou7Haojun Fan8Ning Li9Yanhua Gong10Institute of Disaster and Emergency Medicine, Medical College, Tianjin University, Tianjin 300072, ChinaInstitute of Disaster and Emergency Medicine, Medical College, Tianjin University, Tianjin 300072, ChinaInstitute of Disaster and Emergency Medicine, Medical College, Tianjin University, Tianjin 300072, ChinaInstitute of Disaster and Emergency Medicine, Medical College, Tianjin University, Tianjin 300072, ChinaInstitute of Disaster and Emergency Medicine, Medical College, Tianjin University, Tianjin 300072, ChinaInstitute of Disaster and Emergency Medicine, Medical College, Tianjin University, Tianjin 300072, ChinaInstitute of Disaster and Emergency Medicine, Medical College, Tianjin University, Tianjin 300072, ChinaInstitute of Disaster and Emergency Medicine, Medical College, Tianjin University, Tianjin 300072, ChinaInstitute of Disaster and Emergency Medicine, Medical College, Tianjin University, Tianjin 300072, ChinaInstitute of Disaster and Emergency Medicine, Medical College, Tianjin University, Tianjin 300072, ChinaInstitute of Disaster and Emergency Medicine, Medical College, Tianjin University, Tianjin 300072, ChinaRepetitive low-level blast (rLLB) exposure is a potential risk factor for the health of soldiers or workers who are exposed to it as an occupational characteristic. Alveolar macrophages (AMs) are susceptible to external blast waves and produce pro-inflammatory or anti-inflammatory effects. However, the effect of rLLB exposure on AMs is still unclear. Here, we generated rLLB waves through a miniature manual Reddy-tube and explored their effects on MH-S cell morphology, phenotype transformation, oxidative stress status, and apoptosis by immunofluorescence, real-time quantitative PCR (qPCR), western blotting (WB) and flow cytometry. Ipatasertib (GDC-0068) or PDTC was used to verify the role of the Akt/NF-κB signaling pathway in these processes. Results showed that rLLB treatment could cause morphological irregularities and cytoskeletal disorders in MH-S cells and promote their polarization to the M1 phenotype by increasing iNOS, CD86 and IL-6 expression. The molecular mechanism is through the Akt/NF-κB signaling pathway. Moreover, we found reactive oxygen species (ROS) burst, Ca<sup>2+</sup> accumulation, mitochondrial membrane potential reduction, and early apoptosis of MH-S cells. Taken together, our findings suggest rLLB exposure may cause M1 polarization and early apoptosis of AMs. Fortunately, it is blocked by specific inhibitors GDC-0068 or PDTC. This study provides a new treatment strategy for preventing and alleviating health damage in the occupational population caused by rLLB exposure.https://www.mdpi.com/1422-0067/24/13/10596repetitive low-level blastAkt/NF-κB signaling pathwaymacrophage polarizationearly apoptosisinhibitorimmune homeostasis |
| spellingShingle | Chenhao Geng Xinyue Wang Jiale Chen Na Sun Yuru Wang Zizheng Li Lu Han Shike Hou Haojun Fan Ning Li Yanhua Gong Repetitive Low-Level Blast Exposure via Akt/NF-κB Signaling Pathway Mediates the M1 Polarization of Mouse Alveolar Macrophage MH-S Cells International Journal of Molecular Sciences repetitive low-level blast Akt/NF-κB signaling pathway macrophage polarization early apoptosis inhibitor immune homeostasis |
| title | Repetitive Low-Level Blast Exposure via Akt/NF-κB Signaling Pathway Mediates the M1 Polarization of Mouse Alveolar Macrophage MH-S Cells |
| title_full | Repetitive Low-Level Blast Exposure via Akt/NF-κB Signaling Pathway Mediates the M1 Polarization of Mouse Alveolar Macrophage MH-S Cells |
| title_fullStr | Repetitive Low-Level Blast Exposure via Akt/NF-κB Signaling Pathway Mediates the M1 Polarization of Mouse Alveolar Macrophage MH-S Cells |
| title_full_unstemmed | Repetitive Low-Level Blast Exposure via Akt/NF-κB Signaling Pathway Mediates the M1 Polarization of Mouse Alveolar Macrophage MH-S Cells |
| title_short | Repetitive Low-Level Blast Exposure via Akt/NF-κB Signaling Pathway Mediates the M1 Polarization of Mouse Alveolar Macrophage MH-S Cells |
| title_sort | repetitive low level blast exposure via akt nf κb signaling pathway mediates the m1 polarization of mouse alveolar macrophage mh s cells |
| topic | repetitive low-level blast Akt/NF-κB signaling pathway macrophage polarization early apoptosis inhibitor immune homeostasis |
| url | https://www.mdpi.com/1422-0067/24/13/10596 |
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