Autophagy participates in cockroach allergen-induced lung inflammation through ROS and CaMKII oxidation.

Autophagy participates in pathogenesis of asthma. Amount of studies have conformed that autophagy level increased in asthmatic patients and OVA-induced asthma model. However, the role of autophagy in cockroach(CRE)-induced asthma is unclear. We have discovered that CRE-increased ROS generation and oxCaMKII promoted asthma. We hypothesize that ROS and oxCaMKII could mediate autophagy in CRE-induced allergic inflammation. CRE-induced asthma model was built in WT mice (with or without autophagy inhibitor, 3-MA) or ROS-resistant MMVVδ mice. Lung inflammation, ROS and autophagy level were assessed. Autophagy, oxCaMKII and ROS level were measured in CRE-and CRE/KN-93(CaMKII inhibitor) treated HBE cells. Autophagy level increased in CRE-induced mouse model of asthma. Inhibiting autophagy with 3-MA attenuated CRE-induced inflammatory cells recruitment and mucus secretion, CRE-specific IgG1 and IgE, and Th2 cytokines (IL4, IL-5 and IL13). We also discovered that CRE could induce autophagy in HBE cells through ROS dependent way. Furthermore, CRE could induce oxCaMKII expression in HBE cells, and KN-93 could attenuate CRE-induced autophagy in a dose-dependent way and decrease CRE-indcued ROS generation in vivo. Meanwhile, CRE-treated ROS-resistant MMVVδ mice showed less inflammation and lower level of autophagy compared to WT mice. Collectively, our studies implicated ROS-oxCaMKII loop played an essential role for autophagy in CRE-induced asthma, which may be a therapeutic target for allergic inflammation and asthma.