HMGB1 could restrict 1,3-β-glucan induced mice lung inflammation by affecting Beclin1 and Bcl2 interaction and promoting the autophagy of epithelial cells

Fungi were microorganisms that are ubiquitous in a variety of environments. Inhalation of fungi-contaminated organic dust led to hypersensitivity pneumonitis and might eventually cause irreversible pulmonary fibrosis. Studies showed that maintaining the homeostasis of epithelial cells was vital for defending the exogenous fungi invasion. HMGB1-dependent autophagy played a critical role in maintaining cell homeostasis in multiple inflammatory diseases. However, the actual role of HMGB1-dependent autophagy in hypersensitivity pneumonitis was unclear. In our study, mice were exposed to 0.3 mg/50 μL 1,3-β-glucan solution by intratracheal instillation to set up the lung inflammation model. To investigate the role of HMGB1-dependent autophagy in 1,3-β-glucan induced lung inflammation, AAV-sh-HMGB1 was intratracheally injected to silence HMGB1 in the lung. Our finding suggested that silencing HMGB1 could aggravate the 1,3-β-glucan induced lung inflammation by inhibiting the autophagy of epithelial cells. And ubiquitination of Beclin1 contributed to decreasing the interaction of Beclin1 and Bcl2, which might be a key regulatory mechanism of HMGB1 on 1,3-β-glucan induced autophagy