Deletion of Nrf2 Enhances Susceptibility to Sinonasal Inflammation After Short-Term PM(2.5) Exposure.

BACKGROUND: Particulate matter 2.5 (PM(2.5)) has been identified as one of the most pathogenic components of air pollution and has been associated with chronic rhinosinusitis (CRS) prevalence and severity.  Nuclear erythroid 2-related factor 2 (Nrf2), an antioxidant transcription factor, is critical for protective responses against environmental exposures, such as PM(2.5). The goal of this study was to elucidate the role of Nrf2 in a short-term PM(2.5)-induced murine model of CRS. METHODS: C57BL/6 wild-type (n = 12) and Nrf2-deficient (n = 12) mice were intranasally challenged with 400 µg of PM(2.5) or saline alone for 2 weeks. Heads were harvested and sectioned to perform IHC and flow cytometry, and sinonasal mucosa was dissected to perform qPCR. RESULTS: Nrf2(-/-) mice exhibited a 50% increase in sinonasal inflammation, with a neutrophilic predominance. Nrf2 deficiency also promoted elevated levels of sinonasal Muc5ac expression and increased expression of type 2, type 3, and epithelial-derived cytokines. CONCLUSION: This study demonstrates that the Nrf2 antioxidant pathway is critical in controlling short-term PM(2.5)-induced sinonasal type 3 inflammation and may represent a potential therapeutic target to modulate the inflammatory response induced by air pollution.  This is the first study to our knowledge to demonstrate that Nrf2 regulates PM(2.5)-induced rhinosinusitis in vivo.