Inflammatory Molecule Elaboration in Secondhand Smoke (SHS)-Induced or Conditional RAGE Transgenic Modeling of Chronic Rhinosinusitis (CRS).

Abstract

Chronic rhinosinusitis (CRS) is characterized by sinonasal inflammation, mucus overproduction, and edematous mucosal tissue. This inflammatory condition is characterized by mucosal thickening, nasal obstruction, facial pain or pressure, hyposmia, and nasal discharge. The aim of this research was to clarify a potential role for the receptor for advanced glycation end-products (RAGE) in mouse nasoantral epithelium in perpetuating pro-inflammatory cytokine elaboration similarly expressed by CRS patients. Specifically, wild-type (WT) mice and transgenic (TG) mice overexpressing RAGE in sinonasal epithelium (RAGE TG mice) were maintained in room air or subjected to secondhand smoke exposure using a nose-only delivery system (Scireq Scientific, Montreal, QC, Canada) for five days per week over a 30-day period. Histological analysis was performed using staining for RAGE. Tissue lysates were analyzed for pro-inflammatory cytokines. We observed increased RAGE expression in sinus tissue following SHS exposure and in sinuses from RAGE TG mice in the absence of SHS. We also discovered elevated T helper (Th)1 products (TNF-α, IL-1β, IFN-γ) and Th2/Th17 (IL-5, IL-13, IL-17A) cytokine abundance in SHS-exposed WT and SHS-exposed RTG tissues compared to room air controls. These findings highlight the pivotal role of RAGE signaling in the exacerbation of inflammatory processes, particularly in the context of chronic inflammation induced by smoke exposure. The study expands our understanding of the RAGE signaling axis as a key contributor to the progression of smoke-related lung and sinonasal pathologies. Targeting RAGE-mediated pathways could represent a novel therapeutic strategy to mitigate the progression of chronic sinusitis associated with smoke exposure.