Targeted mice reveal a role for RAGE in an early inflammatory response to tobacco smoke (834.4)

Abstract

The receptor for advanced glycation end‐products (RAGE) has increasingly been demonstrated to be an important modulator of inflammation in cases of pulmonary disease. Published reports involving tobacco smoke exposure have demonstrated increased expression of RAGE, its participation in pro‐inflammatory signaling and its role in irreversible pulmonary remodeling. The current research evaluated the in vivo effects of short‐term tobacco smoke exposure in RAGE null and control mice compared to identical animals groups exposed to room air only. Q‐PCR and immunoblotting revealed elevated RAGE expression in controls after four weeks of exposure and an anticipated absence of RAGE expression in RAGE null mice regardless of smoke exposure. Inflammatory cell behaviors were assessed by determining the activation of ras, intracellular signaling kinases, and cytokine synthesis and secretion. Furthermore, bronchoalveolar lavage fluid (BALF) was procured from RAGE null and control animals prior to assessment for inflammatory cells and molecules. As a general theme, inflammation induced by tobacco smoke exposure was influenced by the availability of RAGE. These data reveal captivating information suggesting a role for RAGE signaling in lungs exposed to tobacco smoke and further research is necessary in order to fully explain roles for receptors such as RAGE in cells coping with exposure. Grant Funding Source: Supported by the Flight Attendant’s Medical Research Institute (FAMRI) and a BYU MEG Award (PRR).