Liangzhong Liu , GuangMing Yi , Xiaohong Li , Cai Chen , Kehong Chen , Hengqiu He , Jinjin Li , Fanghao Cai , Yuan Peng , Zhenzhou Yang , Xiaoyue Zhang
{"title":"IL-17A 在加剧辐射诱导的肺损伤中的作用：通过 PP2A-mTOR 通路的自噬损伤","authors":"Liangzhong Liu , GuangMing Yi , Xiaohong Li , Cai Chen , Kehong Chen , Hengqiu He , Jinjin Li , Fanghao Cai , Yuan Peng , Zhenzhou Yang , Xiaoyue Zhang","doi":"10.1016/j.bbamcr.2024.119864","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Radiation-induced lung injury (RILI) is a serious complication of radiotherapy, and the role of IL-17A in this process is not well understood. While IL-17A has been shown to modulate autophagy, conflicting reports exist regarding its activation or inhibition of autophagy. This study investigates the role of IL-17A in RILI and its effects on autophagy via the PP2A-mTOR pathway, with a focus on the PP2A B56α subunit.</div></div><div><h3>Methods</h3><div>C57BL/6J mice and human lung epithelial cells (BEAS-2B) were exposed to radiation with or without recombinant IL-17A. Autophagy markers were analyzed using Western blotting, immunofluorescence, and autophagy flux assays. PP2A activity, specifically the B56α subunit, was measured. A PP2A agonist (DT-061) was used to verify its role in reversing IL-17A-mediated autophagy inhibition.</div></div><div><h3>Results</h3><div>IL-17A inhibited autophagy in lung epithelial cells exposed to radiation by suppressing PP2A activity, particularly through downregulation of the B56α subunit, leading to mTOR activation and reduced autophagosome formation. Treatment with DT-061 restored autophagic activity and improved cell viability. These findings align with reports suggesting that IL-17A inhibits autophagy in certain contexts, while other studies have shown opposing effects.</div></div><div><h3>Conclusion</h3><div>IL-17A inhibits autophagy in RILI through the PP2A B56α-mTOR pathway, exacerbating lung damage. Further research is needed to clarify the role of IL-17A in different cell types and conditions. Targeting the IL-17A-PP2A B56α-mTOR axis may offer new therapeutic strategies for RILI management.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 1","pages":"Article 119864"},"PeriodicalIF":4.6000,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"IL-17A's role in exacerbating radiation-induced lung injury: Autophagy impairment via the PP2A-mTOR pathway\",\"authors\":\"Liangzhong Liu , GuangMing Yi , Xiaohong Li , Cai Chen , Kehong Chen , Hengqiu He , Jinjin Li , Fanghao Cai , Yuan Peng , Zhenzhou Yang , Xiaoyue Zhang\",\"doi\":\"10.1016/j.bbamcr.2024.119864\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><div>Radiation-induced lung injury (RILI) is a serious complication of radiotherapy, and the role of IL-17A in this process is not well understood. While IL-17A has been shown to modulate autophagy, conflicting reports exist regarding its activation or inhibition of autophagy. This study investigates the role of IL-17A in RILI and its effects on autophagy via the PP2A-mTOR pathway, with a focus on the PP2A B56α subunit.</div></div><div><h3>Methods</h3><div>C57BL/6J mice and human lung epithelial cells (BEAS-2B) were exposed to radiation with or without recombinant IL-17A. Autophagy markers were analyzed using Western blotting, immunofluorescence, and autophagy flux assays. PP2A activity, specifically the B56α subunit, was measured. A PP2A agonist (DT-061) was used to verify its role in reversing IL-17A-mediated autophagy inhibition.</div></div><div><h3>Results</h3><div>IL-17A inhibited autophagy in lung epithelial cells exposed to radiation by suppressing PP2A activity, particularly through downregulation of the B56α subunit, leading to mTOR activation and reduced autophagosome formation. Treatment with DT-061 restored autophagic activity and improved cell viability. These findings align with reports suggesting that IL-17A inhibits autophagy in certain contexts, while other studies have shown opposing effects.</div></div><div><h3>Conclusion</h3><div>IL-17A inhibits autophagy in RILI through the PP2A B56α-mTOR pathway, exacerbating lung damage. Further research is needed to clarify the role of IL-17A in different cell types and conditions. Targeting the IL-17A-PP2A B56α-mTOR axis may offer new therapeutic strategies for RILI management.</div></div>\",\"PeriodicalId\":8754,\"journal\":{\"name\":\"Biochimica et biophysica acta. 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Molecular cell research","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0167488924002076","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
IL-17A's role in exacerbating radiation-induced lung injury: Autophagy impairment via the PP2A-mTOR pathway
Objective
Radiation-induced lung injury (RILI) is a serious complication of radiotherapy, and the role of IL-17A in this process is not well understood. While IL-17A has been shown to modulate autophagy, conflicting reports exist regarding its activation or inhibition of autophagy. This study investigates the role of IL-17A in RILI and its effects on autophagy via the PP2A-mTOR pathway, with a focus on the PP2A B56α subunit.
Methods
C57BL/6J mice and human lung epithelial cells (BEAS-2B) were exposed to radiation with or without recombinant IL-17A. Autophagy markers were analyzed using Western blotting, immunofluorescence, and autophagy flux assays. PP2A activity, specifically the B56α subunit, was measured. A PP2A agonist (DT-061) was used to verify its role in reversing IL-17A-mediated autophagy inhibition.
Results
IL-17A inhibited autophagy in lung epithelial cells exposed to radiation by suppressing PP2A activity, particularly through downregulation of the B56α subunit, leading to mTOR activation and reduced autophagosome formation. Treatment with DT-061 restored autophagic activity and improved cell viability. These findings align with reports suggesting that IL-17A inhibits autophagy in certain contexts, while other studies have shown opposing effects.
Conclusion
IL-17A inhibits autophagy in RILI through the PP2A B56α-mTOR pathway, exacerbating lung damage. Further research is needed to clarify the role of IL-17A in different cell types and conditions. Targeting the IL-17A-PP2A B56α-mTOR axis may offer new therapeutic strategies for RILI management.
期刊介绍：
BBA Molecular Cell Research focuses on understanding the mechanisms of cellular processes at the molecular level. These include aspects of cellular signaling, signal transduction, cell cycle, apoptosis, intracellular trafficking, secretory and endocytic pathways, biogenesis of cell organelles, cytoskeletal structures, cellular interactions, cell/tissue differentiation and cellular enzymology. Also included are studies at the interface between Cell Biology and Biophysics which apply for example novel imaging methods for characterizing cellular processes.
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