HIF-1α promotes NLRP3 inflammasome activation in bleomycin-induced acute lung injury

The inflammatory response is one of the most important factors in the occurrence and development of acute lung injury (ALI). Hypoxia-inducible factor-1 alpha (HIF-1 alpha) and the NOD-like receptor 3 (NLRP3) inflammasome have been demonstrated to serve an important role in the pathogenesis of ALI. The objective of the present study was to investigate whether HIF-1 alpha could regulate activation of the NLRP3 inflammasome and its potential function and specific mechanism in bleomycin (BLM)-induced ALI. Activation of the NLRP3 inflammasome and secretion of IL-1 beta were detected following silencing of HIF-1 alpha or NF-kappa B, respectively, in BLM-treated A549 and RLE-6TN cells. The results demonstrated that the NLRP3 inflammasome could be activated after BLM treatment. HIF-1 alpha and NF-kappa B expression significantly increased in the BLM group. The levels of NF-kappa B- and NLRP3 inflammasome-associated proteins, including NLRP3, apoptosis-associated speck-like protein containing CARD and caspase-1, markedly decreased after treating A549 and RLE-6TN cells with HIF-1 alpha small interfering RNA. Activation of the NLRP3 inflammasome was also inhibited after silencing NF-kappa B. Furthermore, the levels of IL-1 beta markedly decreased in the cellular culture supernatants following inhibition of HIF-1 alpha and NF-kappa B. Therefore, the present study indicated that HIF-1 alpha could modulate the activation of the NLRP3 inflammasome and the secretion of IL-1 beta through NF-kappa B signaling in BLM-induced ALI. The current results improve understanding of the mechanism of ALI and may provide new ideas for identifying therapeutic targets of ALI.