Antenatal exposure of maternal secondhand smoke (SHS) increases fetal lung expression of RAGE and induces RAGE-mediated pulmonary inflammation

Respiratory Research

Paul R Reynolds¹  Felix R Jimenez¹  Zac R Jergensen¹  Alex J Wright¹  Michael Chavarria¹  Geraldine D Rogers¹  Cameron M Jones¹  Jared S Bodine¹  Bryce C Betteridge¹  David B Barton¹  Duane R Winden¹ 

[1] Department of Physiology and Developmental Biology, Brigham Young University, 375A Widtsoe Building, Provo 84602, UT, USA

关键词: Collagen;    Lung;    Tobacco;    RAGE;   

Others  :  1137250
DOI  :  10.1186/s12931-014-0129-7

 received in 2014-07-30, accepted in 2014-10-13,  发布年份 2014

【 摘 要 】

Background

Receptors for advanced glycation end-products (RAGE) are immunoglobulin-like pattern recognition receptors abundantly localized to lung epithelium. Our research demonstrated that primary tobacco smoke exposure increases RAGE expression and that RAGE partly mediates pro-inflammatory signaling during exposure. However, the degree to which RAGE influences developing lungs when gestating mice are exposed to secondhand smoke (SHS) has not been determined to date.

Methods

Timed pregnant RAGE null and wild type control mice were exposed to 4 consecutive days of SHS from embryonic day (E) 14.5 through E18.5 using a state of the art nose-only smoke exposure system (Scireq, Montreal, Canada). RAGE expression was assessed using immunofluorescence, immunoblotting, and quantitative RT-PCR. TUNEL immunostaining and blotting for caspase-3 were performed to evaluate effects on cell turnover. Matrix abnormalities were discerned by quantifying collagen IV and MMP-9, a matrix metalloprotease capable of degrading basement membranes. Lastly, TNF-α and IL-1β levels were assessed in order to determine inflammatory status in the developing lung.

Results

Pulmonary RAGE expression was elevated in both dams exposed to SHS and in fetuses gestating within mothers exposed to SHS. Fetal weight, a measure of organismal health, was decreased in SHS-exposed pups, but unchanged in SHS-exposed RAGE null mice. TUNEL assessments suggested a shift toward pulmonary cell apoptosis and matrix in SHS-exposed pups was diminished as revealed by decreased collagen IV and increased MMP-9 expression. Furthermore, SHS-exposed RAGE null mice expressed less TNF-α and IL-1β when compared to SHS-exposed controls.

Conclusions

RAGE augmentation in developing pups exposed to maternal SHS weakens matrix deposition and influences lung inflammation.

【 授权许可】

   
2014 Winden et al.; licensee BioMed Central Ltd.

【 图 表 】

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