HMGB1-activatied NLRP3 inflammasome induces thrombocytopenia in heatstroke rat
Background Thrombocytopenia, an early common complication in heatstroke (HS), has been widely considered as a mortality predictor of HS. The mechanism underlying thrombocytopenia in HS remains unknown. It is not known whether NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is...
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PeerJ Inc.
2022-08-01
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| Online Access: | https://peerj.com/articles/13799.pdf |
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| author | Huimei Yin Ming Wu Yong Lu Xinghui Wu BaoJun Yu Ronglin Chen JieFu Lu Huasheng Tong |
| author_facet | Huimei Yin Ming Wu Yong Lu Xinghui Wu BaoJun Yu Ronglin Chen JieFu Lu Huasheng Tong |
| author_sort | Huimei Yin |
| collection | DOAJ |
| description | Background Thrombocytopenia, an early common complication in heatstroke (HS), has been widely considered as a mortality predictor of HS. The mechanism underlying thrombocytopenia in HS remains unknown. It is not known whether NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is activated in HS platelet, which, in turn, induces platelet activation and thrombocytopenia. This study tried to clarify the activation of the NOD-like receptor signaling pathway under HS conditions and investigate its roles in mediating HS-induced thrombocytopenia. Methods Rat HS models were established in a certain ambient temperature and humidity. Platelets, isolated from blood, were counted and CD62P, an index of platelet activation, was measured by flow cytometry in all rats. The colocalization of NLRP3 inflammasome in platelet was detected by confocal fluorescence microscopy. Mitochondrial-derived reactive oxygen species (ROS) was detected using the molecular probes. Plasma HMGB1 and IL-1β levels were measured by ELISA. Results Platelet activation, showed by upregulated CD62P, and thrombocytopenia were observed in HS rats. HS activated the NLRP3 inflammasome, which was induced by elevated levels of ROS, while the upregulated CD62P and thrombocytopenia triggered by NLRP3 inflammasome were attributed to the high mobility group box protein 1 (HMGB1) inplasma. Moreover, inhibition of the NOD-like receptor signaling pathway in rats with HS suppressed platelet activation and the decline of platelet count. Similar results were obtained when the receptor toll-like receptor 4 (TLR4)/advanced glycation end product (RAGE) was blocked. Conclusions The NOD-like receptor signaling pathway induces platelet activation and thrombocytopenia in HS rats. These findings suggested that the NLRP3 inflammasome might be the potential target for HS treatment. |
| first_indexed | 2024-03-09T08:01:19Z |
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| language | English |
| last_indexed | 2024-03-09T08:01:19Z |
| publishDate | 2022-08-01 |
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| spelling | doaj.art-08487487cbc74cc7ab710d4be557cada2023-12-03T00:41:16ZengPeerJ Inc.PeerJ2167-83592022-08-0110e1379910.7717/peerj.13799HMGB1-activatied NLRP3 inflammasome induces thrombocytopenia in heatstroke ratHuimei Yin0Ming Wu1Yong Lu2Xinghui Wu3BaoJun Yu4Ronglin Chen5JieFu Lu6Huasheng Tong7The 3rd Xiangya Hospital, Central South University, Department of Critical Care Medicine and Hematology, Changsha, Hunan, ChinaDepartment of Intensive Care Unit & Infection Prevention and Control, The Second People‘s Hospital of Shenzhen, Shenzhen, Guangdong, ChinaDepartment of Critical Care Medicine, The First People’s Hospital of Chenzhou, Chenzhou, Hunan, ChinaDepartment of Graduate School, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Intensive Care Unit, Baoan District People’s Hospital, Shenzhen, Guangdong, ChinaDepartment of Critical Care Medicine, Longgang District Central Hospital, Shenzhen, Guangdong, ChinaDepartment of Intensive Care Unit, The First People’s Hospital of Foshan, Foshan, Guangdong, ChinaDepartment of Graduate School, Southern Medical University, Guangzhou, Guangdong, ChinaBackground Thrombocytopenia, an early common complication in heatstroke (HS), has been widely considered as a mortality predictor of HS. The mechanism underlying thrombocytopenia in HS remains unknown. It is not known whether NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is activated in HS platelet, which, in turn, induces platelet activation and thrombocytopenia. This study tried to clarify the activation of the NOD-like receptor signaling pathway under HS conditions and investigate its roles in mediating HS-induced thrombocytopenia. Methods Rat HS models were established in a certain ambient temperature and humidity. Platelets, isolated from blood, were counted and CD62P, an index of platelet activation, was measured by flow cytometry in all rats. The colocalization of NLRP3 inflammasome in platelet was detected by confocal fluorescence microscopy. Mitochondrial-derived reactive oxygen species (ROS) was detected using the molecular probes. Plasma HMGB1 and IL-1β levels were measured by ELISA. Results Platelet activation, showed by upregulated CD62P, and thrombocytopenia were observed in HS rats. HS activated the NLRP3 inflammasome, which was induced by elevated levels of ROS, while the upregulated CD62P and thrombocytopenia triggered by NLRP3 inflammasome were attributed to the high mobility group box protein 1 (HMGB1) inplasma. Moreover, inhibition of the NOD-like receptor signaling pathway in rats with HS suppressed platelet activation and the decline of platelet count. Similar results were obtained when the receptor toll-like receptor 4 (TLR4)/advanced glycation end product (RAGE) was blocked. Conclusions The NOD-like receptor signaling pathway induces platelet activation and thrombocytopenia in HS rats. These findings suggested that the NLRP3 inflammasome might be the potential target for HS treatment.https://peerj.com/articles/13799.pdfHeatstrokePlateletNOD-like receptorPyroptosisReactive oxygen speciesNLRP3 inflammasome |
| spellingShingle | Huimei Yin Ming Wu Yong Lu Xinghui Wu BaoJun Yu Ronglin Chen JieFu Lu Huasheng Tong HMGB1-activatied NLRP3 inflammasome induces thrombocytopenia in heatstroke rat PeerJ Heatstroke Platelet NOD-like receptor Pyroptosis Reactive oxygen species NLRP3 inflammasome |
| title | HMGB1-activatied NLRP3 inflammasome induces thrombocytopenia in heatstroke rat |
| title_full | HMGB1-activatied NLRP3 inflammasome induces thrombocytopenia in heatstroke rat |
| title_fullStr | HMGB1-activatied NLRP3 inflammasome induces thrombocytopenia in heatstroke rat |
| title_full_unstemmed | HMGB1-activatied NLRP3 inflammasome induces thrombocytopenia in heatstroke rat |
| title_short | HMGB1-activatied NLRP3 inflammasome induces thrombocytopenia in heatstroke rat |
| title_sort | hmgb1 activatied nlrp3 inflammasome induces thrombocytopenia in heatstroke rat |
| topic | Heatstroke Platelet NOD-like receptor Pyroptosis Reactive oxygen species NLRP3 inflammasome |
| url | https://peerj.com/articles/13799.pdf |
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