Diesel Particulate Matter Induces Receptor for Advanced Glycation End-Products (RAGE) Expression in Pulmonary Epithelial Cells, and RAGE Signaling Influences NF-κB–Mediated Inflammation
نویسندگان
چکیده
BACKGROUND Receptors for advanced glycation end-products (RAGE) are cell-surface receptors expressed by alveolar type I (ATI) epithelial cells and are implicated in mechanisms of alveolar development and sustained pulmonary inflammation. OBJECTIVES In the present study, we tested the hypothesis that diesel particulate matter (DPM) up-regulates RAGE in rat ATI-like R3/1 cells and human primary small airway epithelial cells (SAECs), leading to an inflammatory response. METHODS AND RESULTS Using real-time reverse transcriptase polymerase chain reaction and immunoblotting, we found that RAGE mRNA and protein are up-regulated in cells exposed to DPM for 2 hr. Use of a luciferase reporter containing nuclear factor-κB (NF-κB) response elements revealed decreased NF-κB activation in cells transfected with small interfering RNA (siRNA) for RAGE (siRAGE) before DPM exposure compared with cells transfected with scrambled control siRNA (siControl). In addition, immunostaining revealed diminished nuclear translocation of NF-κB in DPM-exposed cells transfected with siRAGE compared with cells transfected with siControl before DPM stimulation. Enzyme-linked immunosorbent assay demonstrated that in R3/1 cells DPM induced secretion of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), two cytokines induced by NF-κB and associated with leukocyte chemotaxis during an inflammatory response. Incorporating siRAGE was sufficient to significantly decrease DPM-induced MCP-1 and IL-8 secretion compared with cells transfected with siControl. CONCLUSIONS These data offer novel insights into potential mechanisms whereby RAGE influences pulmonary inflammation exacerbated by DPM exposure. Further research may demonstrate that molecules involved in RAGE signaling are potential targets in lessening the degree of particulate matter-induced exacerbations of inflammatory lung disease.
منابع مشابه
Expression of the receptor of advanced glycation end-products (RAGE) and membranal location in peripheral blood mononuclear cells (PBMC) in obesity and insulin resistance
Objective(s): The present study aimed to evaluate the receptor of advanced glycation end-products (RAGE), NF-kB, NRF2 gene expression, and RAGE cell distribution in peripheral blood mononuclear cells (PBMC) in subjects with obesity and IR compared with healthy subjects.Materials and Methods: The mRNA expression levels of RAGE, NF-kB, NRF...
متن کاملAdvanced Glycation End-Products and Their Receptor-Mediated Roles: Inflammation and Oxidative Stress
Glycation is a protein modification, which results in a change in a protein structure. Glycation is believed to be the etiology of various age-related diseases such as diabetes mellitus and Alz-heimer’s disease (AD). Activation of microglia and resident macrophages in the brain by glycated proteins with subsequent oxidative stress and cytokine release may be an important factor in the progressi...
متن کاملRoad RAGE?: The Role of Diesel Particulate Matter in Lung Inflammation
Diesel particulate matter (DPM) is a nearly ubiquitous environmental pollutant. It is known to be inflammatory and is linked to a plethora of health effects including asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. New research sheds light on which components of DPM are harmful to the lung and what mechanisms they trigger [EHP 119(3):332–336; Reynolds et al.]. The authors...
متن کاملEmbryonic overexpression of receptors for advanced glycation end-products by alveolar epithelium induces an imbalance between proliferation and apoptosis.
Receptors for advanced glycation end-products (RAGEs) are multiligand cell surface receptors highly expressed in the lung that contribute to alveolar epithelial cell differentiation during embryogenesis and the modulation of pulmonary inflammation during disease. When RAGEs are overexpressed throughout embryogenesis, severe lung hypoplasia ensues, culminating in perinatal lethality. However, th...
متن کاملAGE-RAGE signal generates a specific NF-κB RelA “barcode” that directs collagen I expression
Advanced glycation end products (AGEs) are sugar-modified biomolecules that accumulate in the body with advancing age, and are implicated in the development of multiple age-associated structural and functional abnormities and diseases. It has been well documented that AGEs signal via their receptor RAGE to activate several cellular programs including NF-κB, leading to inflammation. A large numb...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 119 شماره
صفحات -
تاریخ انتشار 2011