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RAGE signaling influences smoke‐induced secretion of pro‐inflammatory cytokines by primary alveolar macrophages
Author(s) -
Johnson KacyAnn D,
Robinson Adam B.,
Reynolds Paul R.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.656.3
Subject(s) - rage (emotion) , secretion , bronchoalveolar lavage , inflammation , proinflammatory cytokine , immunology , eotaxin , population , receptor , alveolar macrophage , macrophage , chemistry , medicine , lung , biology , endocrinology , chemokine , biochemistry , in vitro , neuroscience , environmental health
Our research has implicated RAGE, a pattern recognition receptor, in inflammation induced by pulmonary epithelial cells exposed to cigarette smoke (CS). However, precise pro‐inflammatory contributions by alveolar macrophages (AMs) in the respiratory compartment remained unknown. Primary AMs were isolated from bronchoalveolar lavage fluid (BALF) and immunohistochemistry was employed using Mac‐3, a macrophage‐specific marker, to ensure the purity of the cell population. Employing quantitative PCR, we discovered that RAGE mRNA was significantly increased by primary AMs from wild type C57Bl/6 mice following CS exposure. Because CS exposure increased RAGE, we exposed freshly isolated primary AMs from RAGE null and wild type mice to CS and assessed pro‐inflammatory molecule secretion. Using a PCR based cDNA amplification approach, we discovered that Eotaxin, IL‐12, and IL‐ 3 were all up‐regulated in wild type primary AMs exposed to CS compared to CS‐exposed AMs from RAGE null mice. Furthermore, ELISAs revealed that RAGE might also regulate the secretion of these pro‐inflammatory cytokines by primary AMs that encounter CS. The data reveal that acute secretion of pro‐inflammatory cytokines by primary AMs exposed to CS occurs, at least in part, via RAGE signaling. This work was supported by a grant from the Flight Attendant's Medical Research Institute (FAMRI, PRR) and a BYU Mentoring Environment Grant (PRR).

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