The HO-1 Signal Prevents HMGB1-Mediated Activation of NLRP3 Inflammasomes in Lipopolysaccharide-Induced Acute Lung Injury In Vitro.

ABSTRACT

BACKGROUND: Current treatments of lipopolysaccharide (LPS)-induced acute lung injury (ALI) are unsatisfactory due to the insufficient understanding of the pathogenesis of LPS-induced ALI. The NLRP3 inflammasome is an essential part of the innate protection system and is involved in LPS-induced ALI; however, comprehensive understanding of molecular pathogenesis of the disease is lacking. Our study explored the effect of heme oxygenase-1 (HO-1) on NLRP3 inflammasomes in vitro. METHODS: Alveolar macrophages (NR8383) were preincubated with high-mobility group box-1 (HMGB1) or HO-1 CRISPR plasmids before LPS stimulation. Then, we detected the effect of HO-1 on NLRP3 inflammasomes. RESULTS: Our study demonstrates that the activation of HO-1 represses the level of NLRP3 inflammasomes and the subsequent increases of the level of IL-1ß. Moreover, NLRP3 inflammasome activation was sensitive to the HMGB1 activity, and HO-1 was able to reduce the amount of HMGB1 released. Furthermore, downregulation of NLRP3 inflammasomes was related to NADPH quinone oxidoreductase 1 (an HO-1-related gene). CONCLUSIONS: Our study clarifies the constrained coordination of the HO-1 signal in the HMGB1-mediated activation of NLRP3 inflammasomes in NR8383 alveolar macrophages after LPS stimulation.