The following is a summary of “Hypoxia-inducible factor 1α activates the NLRP3 inflammasome to regulate epithelial differentiation in chronic rhinosinusitis,” published in the DECEMBER 2023 issue of Allergy & Immunology by Zhong, et al.
Chronic rhinosinusitis (CRS) is characterized by upper airway inflammation, and its association with hypoxia-mediated inflammation remains underexplored. The role of hypoxia-inducible factor 1α (HIF-1α) in activating NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in the pathogenesis of sinonasal mucosa was poorly understood. For a study, researchers sought to investigate the impact and mechanism of HIF-1α on the activation of NLRP3 inflammasome in primary human nasal epithelial cells (hNECs).
The study assessed the expression levels of HIF-1α and the NLRP3 inflammasome in nasal biopsy samples and hNECs obtained from healthy individuals (negative controls) and patients with CRS with and without nasal polyps. The research also delved into the specific mechanism by which HIF-1α regulates the NLRP3 inflammasome and its effects on hNEC differentiation.
Increased mRNA and protein levels of HIF-1α and the NLRP3 inflammasome were observed in all CRS biopsy samples. In hNECs, HIF-1α influenced the expression of phosphorylated NLRP3, promoted the recruitment of caspase-1 and ASC by NLRP3, and enhanced NLRP3 stability, preventing its degradation caused by hypoxia-mediated inflammation. Furthermore, HIF-1α influenced the expression of Mucin5AC and α-tubulin, suggesting an impact on goblet cell proliferation and cilia loss in hNECs. Additionally, HIF-1α directly promoted P63 expression in hNECs.
HIF-1α appeared to play a role in inducing cilia loss and enhancing goblet cell proliferation, potentially mediated through the regulation of NLRP3 phosphorylation in CRS inflammation. The study shed light on the complex interplay between hypoxia, HIF-1α, and NLRP3 inflammasome activation in the pathophysiology of chronic rhinosinusitis.
Source: jacionline.org/article/S0091-6749(23)01201-0/fulltext
