Diesel particulate matter (DPM) induces receptor for advanced glycation end‐products (RAGE) expression by pulmonary macrophages

Abstract

RAGE is a cell‐surface receptor implicated in mechanisms of sustained pulmonary inflammation. In the present study, we tested the hypothesis that diesel particulate matter (DPM) up‐regulates RAGE in pulmonary macrophages (PMs) and influences infammation. Using real time RT‐PCR, we demonstrate that RAGE was up‐regulated in immortalized mouse macrophages (RAW) exposed to DPM for four hours. Because DPM increased RAGE expression, we exposed primary AMs isolated from RAGE null and wild type Balb/C mice to DPM. Immunohistochemistry using Mac‐3, a macrophage‐specific antibody, ensured a pure cell population. Utilization of a reporter vector containing NF‐kB response elements upstream of the luciferase gene revealed that NF‐κB‐mediated inflammation in cells exposed to DPM is mediated in part by RAGE. Lastly, a PCR based cDNA amplification approach revealed that TNF‐α, IL‐4, 5, 12, and 13 were all up‐regulated following DPM exposure which may occur in part through RAGE signaling. Collectively, these data offer insights into potential mechanisms whereby RAGE influences macrophage‐mediated inflammation exacerbated by DPM exposure. Further research may demonstrate RAGE signaling as a potential target in the successful treatment of inflammatory lung diseases. This work was supported by a grant from the Flight Attendant's Medical Research Institute (FAMRI, PRR) and a BYU Mentoring Environment Grant (PRR).