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

  • Authors:
    • Jun‑Jun Huang
    • Jie Xia
    • Li‑Li Huang
    • Ya‑Chun Li
  • View Affiliations

  • Published online on: August 8, 2019     https://doi.org/10.3892/mmr.2019.10575
  • Pages: 3424-3432
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Abstract

The inflammatory response is one of the most important factors in the occurrence and development of acute lung injury (ALI). Hypoxia‑inducible factor‑1α (HIF‑1α) 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‑1α 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‑1β were detected following silencing of HIF‑1α or NF‑κB, respectively, in BLM‑treated A549 and RLE‑6TN cells. The results demonstrated that the NLRP3 inflammasome could be activated after BLM treatment. HIF‑1α and NF‑κB expression significantly increased in the BLM group. The levels of NF‑κB‑ 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‑1α small interfering RNA. Activation of the NLRP3 inflammasome was also inhibited after silencing NF‑κB. Furthermore, the levels of IL‑1β markedly decreased in the cellular culture supernatants following inhibition of HIF‑1α and NF‑κB. Therefore, the present study indicated that HIF‑1α could modulate the activation of the NLRP3 inflammasome and the secretion of IL‑1β through NF‑κB 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.

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Copy and paste a formatted citation
APA
Huang, J., Xia, J., Huang, L., & Li, Y. (2019). HIF‑1α promotes NLRP3 inflammasome activation in bleomycin‑induced acute lung injury. Molecular Medicine Reports, 20, 3424-3432. https://doi.org/10.3892/mmr.2019.10575
MLA
Huang, J., Xia, J., Huang, L., Li, Y."HIF‑1α promotes NLRP3 inflammasome activation in bleomycin‑induced acute lung injury". Molecular Medicine Reports 20.4 (2019): 3424-3432.
Chicago
Huang, J., Xia, J., Huang, L., Li, Y."HIF‑1α promotes NLRP3 inflammasome activation in bleomycin‑induced acute lung injury". Molecular Medicine Reports 20, no. 4 (2019): 3424-3432. https://doi.org/10.3892/mmr.2019.10575