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

作者：Winden Duane R; Barton David B; Betteridge Bryce C; Bodine Jared S; Jones Cameron M; Rogers Geraldine D; Chavarria Michael; Wright Alex J; Jergensen Zac R; Jimenez Felix R; Reynolds Paul R^*

来源：Respiratory Research, 2014, 15(1): 129.

DOI：10.1186/s12931-014-0129-7

• RAGE
• Tobacco
• Lung
• Collagen

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. %26lt;br%26gt;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-alpha and IL-1 beta levels were assessed in order to determine inflammatory status in the developing lung. %26lt;br%26gt;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-alpha and IL-1 beta when compared to SHS-exposed controls. %26lt;br%26gt;Conclusions: RAGE augmentation in developing pups exposed to maternal SHS weakens matrix deposition and influences lung inflammation.

• 出版日期2014-10-23