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

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.

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