Maternal smoking and the retinoid pathway in the developing lung

Respiratory Research

Kathleen J Haley²  Rebecca M Baron²  Wellington V Cardoso¹  Yolanda Porrata²  Chang Hyeok An²  Carrie A Vyhlidal³  Lacey A Smith²  Sara E Manoli² 

[1] Pulmonary Center of Boston University School of Medicine, Boston, MA, USA;Department of Medicine, Division of Pulmonary and Critical Care, Brigham and Women’s Hospital, Boston, MA, USA;Division of Pediatric Clinical Pharmacology, Children’s Mercy Hospital and Clinics, Kansas City, MO, USA

关键词: Retinoic acid;    Lung development;    Maternal smoking;   

Others  :  796719
DOI  :  10.1186/1465-9921-13-42

 received in 2012-01-11, accepted in 2012-04-30,  发布年份 2012

【 摘 要 】

Background

Maternal smoking is a risk factor for pediatric lung disease, including asthma. Animal models suggest that maternal smoking causes defective alveolarization in the offspring. Retinoic acid signaling modulates both lung development and postnatal immune function. Thus, abnormalities in this pathway could mediate maternal smoking effects. We tested whether maternal smoking disrupts retinoic acid pathway expression and functioning in a murine model.

Methods

Female C57Bl/6 mice with/without mainstream cigarette smoke exposure (3 research cigarettes a day, 5 days a week) were mated to nonsmoking males. Cigarette smoke exposure continued throughout the pregnancy and after parturition. Lung tissue from the offspring was examined by mean linear intercept analysis and by quantitative PCR. Cell culture experiments using the type II cell-like cell line, A549, tested whether lipid-soluble cigarette smoke components affected binding and activation of retinoic acid response elements in vitro.

Results

Compared to tobacco-naïve mice, juvenile mice with tobacco toxin exposure had significantly (P < 0.05) increased mean linear intercepts, consistent with an alveolarization defect. Tobacco toxin exposure significantly (P < 0.05) decreased mRNA and protein expression of retinoic acid signaling pathway elements, including retinoic acid receptor alpha and retinoic acid receptor beta, with the greatest number of changes observed between postnatal days 3–5. Lipid-soluble cigarette smoke components significantly (P < 0.05) decreased retinoic acid-induced binding and activation of the retinoic acid receptor response element in A549 cells.

Conclusions

A murine model of maternal cigarette smoking causes abnormal alveolarization in association with altered retinoic acid pathway element expression in the offspring. An in vitro cell culture model shows that lipid-soluble components of cigarette smoke decrease retinoic acid response element activation. It is feasible that disruption of retinoic acid signaling contributes to the pediatric lung dysfunction caused by maternal smoking.

【 授权许可】

   
2012 Manoli et al.; licensee BioMed Central Ltd.

【 图 表 】

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