Related Experiment Video
Updated: Apr 21, 2026
An IL-8 Transiently Transgenized Mouse Model for the In Vivo Long-term Monitoring of Inflammatory Responses
Published on: July 7, 2017
Conditionally induced RAGE expression by proximal airway epithelial cells in transgenic mice causes lung inflammation
B Garrett Bodine1, Brock G Bennion2, Emma Leatham3
1Department of Physiology and Developmental Biology, Brigham Young University, 3054 Life Sciences Building, Provo, UT, 84602, USA. gbodine14@gmail.com.
Background:
Receptors for advanced glycation end-products (RAGE) are multiligand cell-surface receptors expressed abundantly by distal pulmonary epithelium. Our lab has discovered RAGE-mediated effects in the orchestration of lung inflammation induced by tobacco smoke and environmental pollutants; however, the specific contribution of RAGE to the progression of proximal airway inflammation is still inadequately characterized.
Methods And Results:
We generated a Tet-inducible transgenic mouse that conditionally overexpressed RAGE using the club cell (Clara) secretory protein (CCSP) promoter expressed by club (Clara) cells localized to the proximal airway. RAGE was induced for 40 days from weaning (20 days of age) until sacrifice date at 60 days. Immunohistochemistry, immunoblotting, and qPCR revealed significant RAGE up-regulation when compared to non-transgenic controls; however, H&E staining revealed no detectible morphological abnormalities and apoptosis was not enhanced during the 40 days of augmentation. Freshly procured bronchoalveolar lavage fluid (BALF) from CCSP-RAGE TG mice had significantly more total leukocytes and PMNs compared to age-matched control littermates. Furthermore, CCSP-RAGE TG mice expressed significantly more tumor necrosis factor alpha (TNF-α), interleukin 7 (IL-7), and interleukin 14 (IL-14) in whole lung homogenates compared to controls.
Conclusions:
These data support the concept that RAGE up-regulation specifically in lung airways may function in the progression of proximal airway inflammation.
Insights
Upregulating Receptors for Advanced Glycation End-products (RAGE) in lung airways of mice increased inflammation. This suggests RAGE plays a role in proximal airway inflammation progression, impacting leukocyte and cytokine levels.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Immunology
Background:
- Receptors for Advanced Glycation End-products (RAGE) are cell-surface receptors abundant in lung epithelium.
- RAGE mediates lung inflammation from environmental factors, but its role in proximal airway inflammation is unclear.
Purpose of the Study:
- To investigate the specific contribution of RAGE to proximal airway inflammation.
Main Methods:
- Generated a Tet-inducible transgenic mouse model overexpressing RAGE in club cells (CCSP promoter).
- Induced RAGE overexpression for 40 days from weaning.
- Analyzed RAGE levels, lung morphology, apoptosis, bronchoalveolar lavage fluid (BALF), and whole lung homogenates.
Main Results:
- Confirmed significant RAGE up-regulation without morphological changes or enhanced apoptosis.
- Observed increased leukocytes and neutrophils in BALF of RAGE-overexpressing mice.
- Detected elevated levels of TNF-α, IL-7, and IL-14 in whole lung homogenates.
Conclusions:
- RAGE up-regulation in lung airways contributes to proximal airway inflammation.
- RAGE signaling impacts inflammatory cell recruitment and cytokine production in the proximal airways.
