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Am J Physiol Lung Cell Mol Physiol. 2014 Nov 15;307(10):L758-64. doi: 10.1152/ajplung.00185.2014. Epub 2014 Sep 26.

Acute secondhand smoke-induced pulmonary inflammation is diminished in RAGE knockout mice.

Author information

1
Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah.
2
Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah paul_reynolds@byu.edu.

Abstract

The receptor for advanced glycation end-products (RAGE) has increasingly been demonstrated to be an important modulator of inflammation in cases of pulmonary disease. Published reports involving tobacco smoke exposure have demonstrated increased expression of RAGE, its participation in proinflammatory signaling, and its role in irreversible pulmonary remodeling. The current research evaluated the in vivo effects of short-term secondhand smoke (SHS) exposure in RAGE knockout and control mice compared with identical animals exposed to room air only. Quantitative PCR, immunoblotting, and immunohistochemistry revealed elevated RAGE expression in controls after 4 wk of SHS exposure and an anticipated absence of RAGE expression in RAGE knockout mice regardless of smoke exposure. Ras activation, NF-κB activity, and cytokine elaboration were assessed to characterize the molecular basis of SHS-induced inflammation in the mouse lung. Furthermore, bronchoalveolar lavage fluid was procured from RAGE knockout and control animals for the assessment of inflammatory cells and molecules. As a general theme, inflammation coincident with leukocyte recruitment was induced by SHS exposure and significantly influenced by the availability of RAGE. These data reveal captivating information suggesting a role for RAGE signaling in lungs exposed to SHS. However, ongoing research is still warranted to fully explain roles for RAGE and other receptors in cells coping with involuntary smoke exposure for prolonged periods of time.

KEYWORDS:

RAGE; inflammation; lung; secondhand smoke

PMID:
25260756
DOI:
10.1152/ajplung.00185.2014
[Indexed for MEDLINE]
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