Deletion of Nrf2 Enhances Susceptibility to Sinonasal Inflammation After Short-Term PM_2.5 Exposure

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.

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.

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.

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.