Plausible Roles for RAGE in Conditions Exacerbated by Direct and Indirect (Secondhand) Smoke Exposure

Abstract

Approximately 1 billion people smoke worldwide, and the burden placed on society by primary and secondhand smokers is expected to increase. Smoking is the leading risk factor for myriad health complications stemming from diverse pathogenic programs. First-and second-hand cigarette smoke contains thousands of constituents, including several carcinogens and cytotoxic chemicals that orchestrate chronic inflammatory responses and destructive remodeling events. In the current review, we outline details related to compromised pulmonary and systemic conditions related to smoke exposure. Specifically, data are discussed relative to impaired lung physiology, cancer mechanisms, maternal-fetal complications, cardiometabolic, and joint disorders in the context of smoke exposure exacerbations. As a general unifying mechanism, the receptor for advanced glycation end-products (RAGE) and its signaling axis is increasingly considered central to smoke-related pathogenesis. RAGE is a multi-ligand cell surface receptor whose expression increases following cigarette smoke exposure. RAGE signaling participates in the underpinning of inflammatory mechanisms mediated by requisite cytokines, chemokines, and remodeling enzymes. Understanding the biological contributions of RAGE during cigarette smoke-induced inflammation may provide critically important insight into the pathology of lung disease and systemic complications that combine during the demise of those exposed.

Mechanisms of vascular comorbidity in autoimmune diseases

“…In autoimmune diseases, smoking was shown to modulate the immune system in various ways, namely the induction of the inflammatory response, alteration of cytokine balance, induction of apoptosis, and DNA damage resulting in the formation of anti-DNA antibodies [ 15 ]. There are a variety of studies that have addressed this area [ 16 – 18 ]. The harmful effect of smoking has been described in early atherogenesis especially on endothelial cells [ 19 ].…”

Cigarette smoke extract induces oral squamous cell carcinoma cell invasion in a receptor for advanced glycation end‐products‐dependent manner

“…Furthermore, decreased Ras activity and decreased invasion observed during RAGE amelioration suggest a RAGE‐dependent signaling program in these cells during exposure to cigarette smoke extract. During RAGE signaling, Ras activation leads to the activation of ERK and/or AKT signaling intermediates . Studies on OSCC show that downregulation of ERK and AKT by different experimental conditions results in decreased proliferation, migration, and invasion, while increased activation of these signaling molecules is associated with increased malignancy of squamous cell carcinoma .…”

Insights into the pathogenesis of nicotine addiction. Could a salivary biosensor be useful in Nicotine Replacement Therapy (NRT)?

“…There were no exclusion criteria concerning the study design. with, which can also be inhaled, absorbed through the skin, or ingested (4). THS, also named Residual tobacco smoke or Aged tobacco smoke, has been measured using liquid or gas chromatography, along with mass spectrometry and has a 6-month lifetime in indoor spaces and on surfaces.…”