Conditionally induced RAGE expression by proximal airway epithelial cells in transgenic mice causes lung inflammation

Respiratory Research

Paul R Reynolds¹  Steven M Knapp¹  Jeff P Johnson¹  Cameron M Jones¹  Connor J Erickson¹  Zac R Jergensen¹  Alex J Wright¹  Felix R Jimenez¹  Emma Leatham¹  Brock G Bennion¹  B Garrett Bodine¹ 

[1] Department of Physiology and Developmental Biology, Brigham Young University, 3054 Life Sciences Building, Provo 84602, UT, USA

关键词: Inflammation;    Lung;    CCSP;    Transgenic;    RAGE;   

Others  :  1137247
DOI  :  10.1186/s12931-014-0133-y

 received in 2014-06-26, accepted in 2014-10-16,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Bodine et al.; licensee BioMed Central Ltd.

【 图 表 】

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