Xiaofei Huang , Man Niu , Tianjing Sun , Mo Li , Xuheng Jiang , Haizhen Duan , Tianxi Zhang , Ji Zhang , Fangke Xie , Renjie Song , Anyong Yu
{"title":"x射线照射通过抑制巨噬细胞中TWIK2活性来减少atp依赖性NLRP3炎性体的激活。","authors":"Xiaofei Huang , Man Niu , Tianjing Sun , Mo Li , Xuheng Jiang , Haizhen Duan , Tianxi Zhang , Ji Zhang , Fangke Xie , Renjie Song , Anyong Yu","doi":"10.1016/j.imlet.2024.106967","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>The spleen, as the body's largest peripheral immune organ and a crucial source of circulating monocytes, plays a significant role in the acute inflammatory response of spleen-derived macrophages to diseases. Therefore, studying the impact and mechanism of X-ray irradiation on spleen-derived macrophages' inflammatory responses is of great importance.</div></div><div><h3>Method</h3><div>Extracted and identified mice splenic macrophages were divided into four groups: control group, LPS and ATP co-stimulated non-irradiated group, LPS and ATP co-stimulated group irradiated after 6 h, and LPS and ATP co-stimulated group irradiated after 12 h In the LPS and ATP co-stimulated groups, LPS (1μg/ml) and ATP (5mmol/L) were added to establish an inflammatory model in mice splenic macrophages. The irradiated groups were exposed to a medical linear accelerator (Elekta Synergy), while the non-irradiated groups were placed under the light source for the same duration without irradiation. Protein extraction was performed in each group at 6 h and 12 h post-treatment for subsequent analysis using Western blot, ELISA, RT-qPCR and other relevant methods.</div></div><div><h3>Results</h3><div>(1) Compared with the non-irradiated group, the cell activity in the groups irradiated for 6 h and 12 h at 8 Gy showed a significant increase (<em>P</em><0.01). (2) In the LPS and ATP co-stimulated groups irradiated after 6 h and 12 h, the expression of NLRP3 mRNA and protein, IL-18 and IL-1β showed a notable decrease compared to the LPS and ATP co-stimulated non-irradiated group (<em>P</em><0.05). Additionally, caspase-1 expression of caspase-1 mRNA and protein in the 12 h post-irradiation group also decreased considerably when compared with the LPS and ATP co-stimulated non-irradiated group (<em>P</em> < 0.05). In the groups irradiated after 6 h and 12 h, (3) there was a remarkable decrease in the expression of TWIK mRNA and TWIK2, (4) as well as Gq mRNA and protein, when compared to the LPS and ATP co-stimulated non-irradiated group (<em>P</em> < 0.05). Particularly, the 12 h post-irradiation group exhibited a notable reduction in PKC expression (<em>P</em> < 0.05).</div></div><div><h3>Conclusion</h3><div>X-ray irradiation is capable of inhibiting the activation of ATP-dependent NLRP3 inflammasomes in splenic macrophages.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"272 ","pages":"Article 106967"},"PeriodicalIF":3.3000,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"X-ray irradiation reduces ATP-dependent activation of NLRP3 inflammasome by inhibiting TWIK2 activity in macrophages\",\"authors\":\"Xiaofei Huang , Man Niu , Tianjing Sun , Mo Li , Xuheng Jiang , Haizhen Duan , Tianxi Zhang , Ji Zhang , Fangke Xie , Renjie Song , Anyong Yu\",\"doi\":\"10.1016/j.imlet.2024.106967\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>The spleen, as the body's largest peripheral immune organ and a crucial source of circulating monocytes, plays a significant role in the acute inflammatory response of spleen-derived macrophages to diseases. Therefore, studying the impact and mechanism of X-ray irradiation on spleen-derived macrophages' inflammatory responses is of great importance.</div></div><div><h3>Method</h3><div>Extracted and identified mice splenic macrophages were divided into four groups: control group, LPS and ATP co-stimulated non-irradiated group, LPS and ATP co-stimulated group irradiated after 6 h, and LPS and ATP co-stimulated group irradiated after 12 h In the LPS and ATP co-stimulated groups, LPS (1μg/ml) and ATP (5mmol/L) were added to establish an inflammatory model in mice splenic macrophages. The irradiated groups were exposed to a medical linear accelerator (Elekta Synergy), while the non-irradiated groups were placed under the light source for the same duration without irradiation. Protein extraction was performed in each group at 6 h and 12 h post-treatment for subsequent analysis using Western blot, ELISA, RT-qPCR and other relevant methods.</div></div><div><h3>Results</h3><div>(1) Compared with the non-irradiated group, the cell activity in the groups irradiated for 6 h and 12 h at 8 Gy showed a significant increase (<em>P</em><0.01). (2) In the LPS and ATP co-stimulated groups irradiated after 6 h and 12 h, the expression of NLRP3 mRNA and protein, IL-18 and IL-1β showed a notable decrease compared to the LPS and ATP co-stimulated non-irradiated group (<em>P</em><0.05). Additionally, caspase-1 expression of caspase-1 mRNA and protein in the 12 h post-irradiation group also decreased considerably when compared with the LPS and ATP co-stimulated non-irradiated group (<em>P</em> < 0.05). In the groups irradiated after 6 h and 12 h, (3) there was a remarkable decrease in the expression of TWIK mRNA and TWIK2, (4) as well as Gq mRNA and protein, when compared to the LPS and ATP co-stimulated non-irradiated group (<em>P</em> < 0.05). Particularly, the 12 h post-irradiation group exhibited a notable reduction in PKC expression (<em>P</em> < 0.05).</div></div><div><h3>Conclusion</h3><div>X-ray irradiation is capable of inhibiting the activation of ATP-dependent NLRP3 inflammasomes in splenic macrophages.</div></div>\",\"PeriodicalId\":13413,\"journal\":{\"name\":\"Immunology letters\",\"volume\":\"272 \",\"pages\":\"Article 106967\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-12-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Immunology letters\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S016524782400141X\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunology letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S016524782400141X","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
X-ray irradiation reduces ATP-dependent activation of NLRP3 inflammasome by inhibiting TWIK2 activity in macrophages
Background
The spleen, as the body's largest peripheral immune organ and a crucial source of circulating monocytes, plays a significant role in the acute inflammatory response of spleen-derived macrophages to diseases. Therefore, studying the impact and mechanism of X-ray irradiation on spleen-derived macrophages' inflammatory responses is of great importance.
Method
Extracted and identified mice splenic macrophages were divided into four groups: control group, LPS and ATP co-stimulated non-irradiated group, LPS and ATP co-stimulated group irradiated after 6 h, and LPS and ATP co-stimulated group irradiated after 12 h In the LPS and ATP co-stimulated groups, LPS (1μg/ml) and ATP (5mmol/L) were added to establish an inflammatory model in mice splenic macrophages. The irradiated groups were exposed to a medical linear accelerator (Elekta Synergy), while the non-irradiated groups were placed under the light source for the same duration without irradiation. Protein extraction was performed in each group at 6 h and 12 h post-treatment for subsequent analysis using Western blot, ELISA, RT-qPCR and other relevant methods.
Results
(1) Compared with the non-irradiated group, the cell activity in the groups irradiated for 6 h and 12 h at 8 Gy showed a significant increase (P<0.01). (2) In the LPS and ATP co-stimulated groups irradiated after 6 h and 12 h, the expression of NLRP3 mRNA and protein, IL-18 and IL-1β showed a notable decrease compared to the LPS and ATP co-stimulated non-irradiated group (P<0.05). Additionally, caspase-1 expression of caspase-1 mRNA and protein in the 12 h post-irradiation group also decreased considerably when compared with the LPS and ATP co-stimulated non-irradiated group (P < 0.05). In the groups irradiated after 6 h and 12 h, (3) there was a remarkable decrease in the expression of TWIK mRNA and TWIK2, (4) as well as Gq mRNA and protein, when compared to the LPS and ATP co-stimulated non-irradiated group (P < 0.05). Particularly, the 12 h post-irradiation group exhibited a notable reduction in PKC expression (P < 0.05).
Conclusion
X-ray irradiation is capable of inhibiting the activation of ATP-dependent NLRP3 inflammasomes in splenic macrophages.
期刊介绍:
Immunology Letters provides a vehicle for the speedy publication of experimental papers, (mini)Reviews and Letters to the Editor addressing all aspects of molecular and cellular immunology. The essential criteria for publication will be clarity, experimental soundness and novelty. Results contradictory to current accepted thinking or ideas divergent from actual dogmas will be considered for publication provided that they are based on solid experimental findings.
Preference will be given to papers of immediate importance to other investigators, either by their experimental data, new ideas or new methodology. Scientific correspondence to the Editor-in-Chief related to the published papers may also be accepted provided that they are short and scientifically relevant to the papers mentioned, in order to provide a continuing forum for discussion.