LAUSR

The receptor for advanced glycation end products (RAGE) is a key contributor to the immune and inflammatory response in a myriad of diseases. RAGE is a transmembrane pattern recognition receptor with special interest in pulmonary anomalies due to its naturally abundant expression in the lungs. Our previous studies demonstrated a role for RAGE in inflammation following acute exposure to secondhand smoke (SHS). However, chronic inflammatory mechanisms associated with RAGE have yet to be fully elucidated. In this study, we address the impact of long-term SHS exposure on RAGE signaling. RAGE knockout (RKO) and wild type (WT) mice were exposed to SHS five times weekly via a nose-only delivery system (Scireq Scientific, Montreal, Canada) for six months. SHS animals were compared to mice exposed to room air only. Immunoblot and colorimetric high throughput FACE assays (Active Motif) were used to assess phospho-AKT and NF-κB, respectively. A mouse cytokine antibody array (Abcam) was used to screen secreted cytokines in bronchoalveolar lavage fluid (BALF). Phospho-AKT was decreased and NF-κB was elevated in both groups of SHS exposed mice, with RKO+SHS mice demonstrating tempered outcomes for both intermediates compared to WT+SHS exposed mice. BALF contained increased levels of pro-inflammatory cytokines including IFNγ, IL-13, MIP-1γ and Eotaxin1 in exposed groups and diminished secretion was observed in exposed RKO mice. These results validate a role for RAGE in the mediation of chronic pulmonary inflammatory responses and suggest AKT signaling as a viable pathway of RAGE dependent inflammatory responses. Additional characterization of RAGE-mediated pulmonary responses to prolonged exposure will provide valuable insight into cellular mechanisms of lung diseases such as chronic obstructive pulmonary disease. This work was supported by funding from the National Institutes of Health (NIH 1R15-HL152257, PRR and JAA). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.