Exposure to toluene diisocyanate (TDI) can cause pulmonary diseases such as asthma. Inhibition of high mobility group box 1 protein (HMGB1) has been found to be protective against the toxic effects of TDI on human bronchial epithelial (HBE) cells. Here, we evaluated the in vivo positive roles of HMGB1 in the TDI-caused asthma mice and explored its underlying mechanisms in HBE cells. We found that suppression of HMGB1 obviously alleviated airway inflammation, airway hyperresponsiveness, and airway remodeling in the lung tissue of the asthma mice. The in vitro results showed that inhibition of HMGB1 ameliorated TDI-induced reactive oxygen species (ROS) release, inflammatory response, and activation of autophagy in HBE cells. At the molecular level, inhibition of HMGB1 decreased the expressions of HMGB1, Toll-like receptor 4, Vimentin and matrix metalloproteinase-9 proteins, activated NF-κB and NOD-like receptor protein 3 (NLRP3) inflammasome, and increased E-cadherin expression. Importantly, activation of autophagy could lead to the overactivation of NLRP3 inflammasome in TDI-induced asthma. These results suggest that inhibition of HMGB1 can alleviate TDI-induced asthma through ROS/AMPK/autophagy pathways, which may provide valuable evidence for the pathogenesis and therapeutic targets of TDI-induced asthma.
Keywords: Airway inflammation; Asthma; Autophagy; High mobility group box 1; Toluene diisocyanate.
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