1. Academic Validation
  2. Interleukin-37 relieves PM2.5-triggered lung injury by inhibiting autophagy through the AKT/mTOR signaling pathway in vivo and in vitro

Interleukin-37 relieves PM2.5-triggered lung injury by inhibiting autophagy through the AKT/mTOR signaling pathway in vivo and in vitro

  • Ecotoxicol Environ Saf. 2023 Dec 12:269:115816. doi: 10.1016/j.ecoenv.2023.115816.
Jing Cao 1 Shujie Hou 1 Zixiao Chen 1 Jie Yan 2 Lingshan Chao 1 Yuxing Qian 1 Jingwen Li 1 Xixin Yan 3
Affiliations

Affiliations

  • 1 The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Respiratory Critical Care Medicine, Hebei Institute of Respiratory Diseases, Shijiazhuang, Hebei 050000, China.
  • 2 Department of Cardiovascular Medicine,The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
  • 3 The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Respiratory Critical Care Medicine, Hebei Institute of Respiratory Diseases, Shijiazhuang, Hebei 050000, China. Electronic address: yanxixin@hebmu.edu.cn.
Abstract

Autophagy mediates PM2.5-related lung injury (LI) and is tightly linked to inflammation and Apoptosis processes. IL-37 has been demonstrated to regulate Autophagy. This research aimed to examine the involvement of IL-37 in the progression of PM2.5-related LI and assess whether Autophagy serves as a mediator for its effects.To create a model of PM2.5-related LI, this research employed a nose-only PM2.5 exposure system and utilized both human IL-37 transgenic mice and wild-type mice. The hIL-37tg mice demonstrated remarkable reductions in pulmonary inflammation and pathological LI compared to the WT mice. Additionally, they exhibited activation of the Akt/mTOR signaling pathway, which served to regulate the levels of Autophagy and Apoptosis.Furthermore, in vitro experiments revealed a dose-dependent upregulation of Autophagy and apoptotic proteins following exposure to PM2.5 DMSO extraction. Simultaneously, p-AKT and p-mTOR expression was found to decrease. However, pretreatment with IL-37 demonstrated a remarkable reduction in the levels of Autophagy and apoptotic proteins, along with an elevation of p-AKT and p-mTOR. Interestingly, pretreatment with rapamycin, an Autophagy inducer, weakened the therapeutic impact of IL-37. Conversely, the therapeutic impact of IL-37 was enhanced when treated with 3-MA, a potent Autophagy Inhibitor. Moreover, the inhibitory effect of IL-37 on Autophagy was successfully reversed by administering Akt Inhibitor MK2206. The findings suggest that IL-37 can inhibit both the inflammatory response and Autophagy, leading to the alleviation of PM2.5-related LI. At the molecular level, IL-37 may exert its anti Autophagy and anti Apoptosis effects by activating the Akt/mTOR signaling pathway.

Keywords

Apoptosis; Autophagy; Fine particulate matter (PM2.5); Interleukin (IL)-37; Lung injury.

Figures
Products