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

• Published in: Ecotoxicology and environmental safety Vol. 269; p. 115816
• Main Authors: Cao, Jing, Hou, Shujie, Chen, Zixiao, Yan, Jie, Chao, Lingshan, Qian, Yuxing, Li, Jingwen, Yan, Xixin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier 01-01-2024
• Subjects: Animals; Apoptosis; Autophagy; Fine particulate matter (PM2.5); Humans; Interleukin (IL)-37; Interleukins - pharmacology; Lung injury; Lung Injury - drug therapy; Mice; Particulate Matter - toxicity; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; Interleukin (IL)-37; Fine particulate matter (PM2.5); Autophagy; Apoptosis; Lung injury
• DOI: 10.1016/j.ecoenv.2023.115816
• EISSN: 1090-2414
• ISSN: 0147-6513

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.