RAGE is a Critical Mediator of Pulmonary Oxidative Stress, Alveolar Macrophage Activation and Emphysema in Response to Cigarette Smoke.
Sci Rep
; 9(1): 231, 2019 01 18.
Article
in En
| MEDLINE
| ID: mdl-30659203
ABSTRACT
The receptor for advanced glycation end products (RAGE), a cell membrane receptor, recognizes ligands produced by cigarette smoke (CS) and has been implicated in the pathogenesis of COPD. We demonstrate that deletion or pharmacologic inhibition of RAGE prevents development of CS-induced emphysema. To identify molecular pathways by which RAGE mediates smoking related lung injury we performed unbiased gene expression profiling of alveolar macrophages (AM) obtained from RAGE null and C57BL/6 WT mice exposed to CS for one week or four months. Pathway analysis of RNA expression identified a number of genes integral to the pathogenesis of COPD impacted by the absence of RAGE. Altered expression of antioxidant response genes and lung protein 4-HNE immunostaining suggest attenuated oxidative stress in the RAGE null mice despite comparable CS exposure and lung leukocyte burden as the WT mice. Reduced endoplasmic reticulum stress in response to CS exposure also was observed in the AM from RAGE null mice. These findings provide novel insight into the sources of oxidative stress, macrophage activation, and the pathogenesis of lung disease due to CS exposure.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Macrophages, Alveolar
/
Oxidative Stress
/
Emphysema
/
Receptor for Advanced Glycation End Products
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Cigarette Smoking
/
Lung
/
Macrophage Activation
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Sci Rep
Year:
2019
Document type:
Article
Affiliation country:
United States