Spatial expression of Receptor for Advanced Glycation End‐Products (RAGE) in diverse tissue and organ systems differs following exposure to secondhand cigarette smoke

Abstract

The receptor for advanced glycation end‐products (RAGE) is a pattern recognition receptor initially identified in the lung and known to be expressed by many cell types including smooth muscle cells, fibroblasts, macrophages/monocytes and epithelial cells. RAGE is capable of binding a variety of endogenous ligands including advanced glycation end‐products (AGEs), S100/calgranulins, amyloid‐β peptide, and HMGB1. Furthermore, exogenous entities such as tobacco smoke particulates also have been demonstrated to activate RAGE and as such, RAGE signaling has been implicated as a major contributor to a variety of inflammatory states. In the present study we examined the expression patterns of RAGE in pulmonary and systemic tissues from mice exposed to room air (RA) and then compared expression with mice following exposure to daily secondhand smoke for up to 6 months via a nose‐only exposure system (Scireq, Montreal, Canada). Following sacrifice, real time PCR revealed interesting expression patterns for RAGE mRNA in tissues and organs such as eyes, lungs, heart, kidney, spleen, gastrocnemius, liver, brain, small intestine, adipose tissue, and dermis. RT‐PCR analysis revealed that augmented RAGE expression is a cellular response to secondhand smoke exposure. Confirmatory studies aimed at characterizing protein levels were also conducted using immunoblot and immunohistochemistry. In conclusion, our data reveal that as already detected in several studies involving the pulmonary apparatus, elevated RAGE expression is a distinct response to smoke exposure and its expression likely elevates the pro‐inflammatory RAGE signaling axis in cells and tissues responding to exposure.Support or Funding InformationThis work was supported by a grant from the Flight Attendant's Medical Research Institute (FAMRI, PRR) and a BYU Mentoring Environment Grant (PRR).