HMGB1 released from pyroptotic vascular endothelial cells promotes immune disorders in exertional heatstroke
Background and objective Exertional heatstroke (EHS) mainly occurs in healthy young people with rapid onset and high mortality. EHS immune disorders can cause systemic inflammatory responses and multiple organ failure; however, the underlying mechanisms remain unclear. As high mobility group box 1 (...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | International Journal of Hyperthermia |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/02656736.2024.2378867 |
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| author | Chaoping Yu Yang Huang Jiangang Xie Chujun Duan Shanshou Liu Wei Zhao Yutong Wang Ran Zhuang Junjie Li Wen Yin |
| author_facet | Chaoping Yu Yang Huang Jiangang Xie Chujun Duan Shanshou Liu Wei Zhao Yutong Wang Ran Zhuang Junjie Li Wen Yin |
| author_sort | Chaoping Yu |
| collection | DOAJ |
| description | Background and objective Exertional heatstroke (EHS) mainly occurs in healthy young people with rapid onset and high mortality. EHS immune disorders can cause systemic inflammatory responses and multiple organ failure; however, the underlying mechanisms remain unclear. As high mobility group box 1 (HMGB1) is a prototypical alarmin that activates inflammatory and immune responses, this study aimed to investigate the effect and mechanism of HMGB1 in the pathogenesis of EHS.Methods Peripheral blood mononuclear cell (PBMC) transcriptome sequencing of healthy volunteers, classical heatstroke patients, and EHS patients was performed. A mouse model of EHS was established and murine tissue damage was evaluated by H&E staining. HMGB1 localization and release were visualized using immunofluorescence staining. Human umbilical vein endothelial cells (HUVECs) and THP-1 cells were co-cultured to study the effects of HMGB1 on macrophages. A neutralizing anti-HMGB1 antibody was used to evaluate the efficacy of EHS treatment in mice.Results Plasma and serum HMGB1 levels were significantly increased in EHS patients or mice. EHS-induced endothelial cell pyroptosis promoted HMGB1 release in mice. HMGB1 derived from endothelial cell pyroptosis enhanced macrophage pyroptosis, resulting in immune disorders under EHS conditions. Administration of anti-HMGB1 markedly alleviated tissue injury and systemic inflammatory responses after EHS.Conclusions The release of HMGB1 from pyroptotic endothelial cells after EHS promotes pyroptosis of macrophages and systemic inflammatory response, and HMGB1-neutralizing antibody therapy has good application prospects for EHS. |
| format | Article |
| id | doaj-art-4cba3633324144929f6df1d5b5f54769 |
| institution | Kabale University |
| issn | 0265-6736 1464-5157 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | International Journal of Hyperthermia |
| spelling | doaj-art-4cba3633324144929f6df1d5b5f547692025-01-03T09:30:28ZengTaylor & Francis GroupInternational Journal of Hyperthermia0265-67361464-51572024-12-0141110.1080/02656736.2024.2378867HMGB1 released from pyroptotic vascular endothelial cells promotes immune disorders in exertional heatstrokeChaoping Yu0Yang Huang1Jiangang Xie2Chujun Duan3Shanshou Liu4Wei Zhao5Yutong Wang6Ran Zhuang7Junjie Li8Wen Yin9Department of Emergency, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaDepartment of Emergency, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaDepartment of Emergency, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaDepartment of Emergency, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaDepartment of Emergency, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaDepartment of Emergency, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaDepartment of Emergency, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaDepartment of Immunology, Fourth Military Medical University, Xi’an, ChinaDepartment of Emergency, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaDepartment of Emergency, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaBackground and objective Exertional heatstroke (EHS) mainly occurs in healthy young people with rapid onset and high mortality. EHS immune disorders can cause systemic inflammatory responses and multiple organ failure; however, the underlying mechanisms remain unclear. As high mobility group box 1 (HMGB1) is a prototypical alarmin that activates inflammatory and immune responses, this study aimed to investigate the effect and mechanism of HMGB1 in the pathogenesis of EHS.Methods Peripheral blood mononuclear cell (PBMC) transcriptome sequencing of healthy volunteers, classical heatstroke patients, and EHS patients was performed. A mouse model of EHS was established and murine tissue damage was evaluated by H&E staining. HMGB1 localization and release were visualized using immunofluorescence staining. Human umbilical vein endothelial cells (HUVECs) and THP-1 cells were co-cultured to study the effects of HMGB1 on macrophages. A neutralizing anti-HMGB1 antibody was used to evaluate the efficacy of EHS treatment in mice.Results Plasma and serum HMGB1 levels were significantly increased in EHS patients or mice. EHS-induced endothelial cell pyroptosis promoted HMGB1 release in mice. HMGB1 derived from endothelial cell pyroptosis enhanced macrophage pyroptosis, resulting in immune disorders under EHS conditions. Administration of anti-HMGB1 markedly alleviated tissue injury and systemic inflammatory responses after EHS.Conclusions The release of HMGB1 from pyroptotic endothelial cells after EHS promotes pyroptosis of macrophages and systemic inflammatory response, and HMGB1-neutralizing antibody therapy has good application prospects for EHS.https://www.tandfonline.com/doi/10.1080/02656736.2024.2378867Exertional heatstrokeHMGB1pyroptosisendothelial cellsmacrophages |
| spellingShingle | Chaoping Yu Yang Huang Jiangang Xie Chujun Duan Shanshou Liu Wei Zhao Yutong Wang Ran Zhuang Junjie Li Wen Yin HMGB1 released from pyroptotic vascular endothelial cells promotes immune disorders in exertional heatstroke International Journal of Hyperthermia Exertional heatstroke HMGB1 pyroptosis endothelial cells macrophages |
| title | HMGB1 released from pyroptotic vascular endothelial cells promotes immune disorders in exertional heatstroke |
| title_full | HMGB1 released from pyroptotic vascular endothelial cells promotes immune disorders in exertional heatstroke |
| title_fullStr | HMGB1 released from pyroptotic vascular endothelial cells promotes immune disorders in exertional heatstroke |
| title_full_unstemmed | HMGB1 released from pyroptotic vascular endothelial cells promotes immune disorders in exertional heatstroke |
| title_short | HMGB1 released from pyroptotic vascular endothelial cells promotes immune disorders in exertional heatstroke |
| title_sort | hmgb1 released from pyroptotic vascular endothelial cells promotes immune disorders in exertional heatstroke |
| topic | Exertional heatstroke HMGB1 pyroptosis endothelial cells macrophages |
| url | https://www.tandfonline.com/doi/10.1080/02656736.2024.2378867 |
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