Mometasone Furoate Alleviates PM2.5-Induced Pyroptosis of Nasal Mucosa Cells via Blocking JAK2/STAT3/AIM2 Inflammasome.

OBJECTIVE

Mometasone furoate (MF) is a widely used intranasal corticosteroid for the management of allergic and non-allergic rhinitis. Recent evidence suggests that its therapeutic efficacy may involve mechanisms beyond traditional anti-inflammatory actions, including modulation of death in nasal mucosa cells. This study aimed to investigate the therapeutic effects of MF on chronic rhinitis, elucidates the underlying molecular mechanisms, and explores its clinical implications in rhinitis management.

METHODS

Enzyme-linked immunosorbent assay was used to detect cytokine release. Reverse transcription quantitative PCR was applied for detecting mRNA expression. Immunofluorescence was used detect LC3 expression. Protein express was detected using Western blot. Lactate dehydrogenase leakage assay was used to detect cytotoxicity. Terminal deoxynucleotidyl transferase dUTP nick-end labeling assay was used to detect death of nasal mucosa cells (NMCs). Luciferase and chromatin immunoprecipitation assays were used to verify the interaction between signal transducer and activator of transcription 3 (STAT3) and absent in melanoma 2 (AIM2).

RESULTS

MF significantly suppressed inflammatory response induced by PM2.5. MF suppressed PM2.5-induced cytotoxicity and pyroptosis of NMCs. Moreover, MF promotes the activation of autophagy. Mechanically, MF inhibited PM2.5-induced activation of Janus kinase 2/STAT3 signaling. STAT3 transcriptionally upregulated AIM2. The activation of AIM2 inflammasome attenuated the effects of MF and promoted the inflammation and pyroptosis of NMCs as well as suppressed the activation of autophagy.

CONCLUSION

In summary, MF protects against chronic rhinitis via suppressing AIM2-dependent pyroptosis of NMCs. Therefore, MF can be a therapeutic strategy for chronic rhinitis.