2. Academic Validation
  3. IL-17A's role in exacerbating radiation-induced lung injury: Autophagy impairment via the PP2A-mTOR pathway

IL-17A's role in exacerbating radiation-induced lung injury: Autophagy impairment via the PP2A-mTOR pathway

  • Biochim Biophys Acta Mol Cell Res. 2024 Oct 20;1872(1):119864. doi: 10.1016/j.bbamcr.2024.119864.
Liangzhong Liu 1,  GuangMing Yi 2,  Xiaohong Li 3,  Cai Chen 2,  Kehong Chen 2,  Hengqiu He 2,  Jinjin Li 2,  Fanghao Cai 2,  Yuan Peng 2,  Zhenzhou Yang 4,  Xiaoyue Zhang 5
Affiliations

Affiliations

  • 1 Department of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China; Department of Oncology, Chongqing University Three Gorges Hospital, Chongqing University, Chongqing 404100, China.
  • 2 Department of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
  • 3 Nursing Department, Chongqing University Three Gorges Hospital, Chongqing University, Chongqing 404100, China.
  • 4 Department of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. Electronic address: yangzz@cqmu.edu.cn.
  • 5 Department of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. Electronic address: xyzhang@cqmu.edu.cn.
PMID: 39437853 DOI: 10.1016/j.bbamcr.2024.119864
Abstract

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.

Keywords

Autophagy; IL-17A; PP2A B56α; Radiation-induced lung injury; mTOR.

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