Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5685121 | Translational Research | 2016 | 30 Pages |
Abstract
Female smokers have a faster decline in lung function with increasing age and overall develop a greater loss of lung function than male smokers. This raises the question of whether estrogen status in women affects susceptibility to cigarette smoke (CS)-induced lung disease. Mouse models suggest that female mice are more susceptible than males to CS-induced lung disease. Moreover, young CS-exposed female mice develop emphysema earlier than male mice. The purpose of this study was to characterize the relationship of estrogen status on the pattern and severity of CS-induced lung disease. In this study, 15-month-old female C57BL/6J mice were ovariectomized and administered either placebo (pla) or 17β-estradiol (E2, 0.025 mg) 2 weeks after ovariectomy. They were further divided into those that were exposed to CS and no-smoke controls (NSC). Mice were exposed to CS in stainless steel inhalation chambers 3 hours a day, 5 days a week for 6 months, and sacrificed after 24 weeks of CS exposure. Blood and urine were collected at sacrifice to measure estrogen and cotinine levels, a metabolite of nicotine. Uterine weight was recorded as an indicator of estrogen status. Results showed that CS in the absence of E2 induced a decrease in hydroxyproline content, macrophage number, and respiratory chain complex-1 protein. CS without E2 also resulted in an increase in matrix metalloproteinase-2 activity and apoptosis and a change in the ratio of estrogen receptor subtype. These findings were abrogated with administration of E2, suggesting that estrogen deficiency increases susceptibility to CS-induced lung disease.
Keywords
ECMNSCCyPPLAHClTSPTNFαPBSMMPMCP-1CML17β-estradiolROShydrochloric acidCOPDChronic obstructive pulmonary diseaseanalysis of varianceANOVAEnzyme-linked immunosorbent assayELISAtumor necrosis factor alphaTUNELCigarette smokeTIMPCytochrome P450Extracellular matrixterminal deoxynucleotidyl transferase-mediated dUTP nick-end labelingMatrix metalloproteinasesPhosphate-buffered salinecarbon monoxideTissue inhibitor of metalloproteinasesmonocyte chemotactic protein 1Placebototal suspended particulateReactive oxygen speciesEstrogen receptor
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Authors
Marilyn K. Glassberg, Paola Catanuto, Shahriar Shahzeidi, Muddassir Aliniazee, Sarit Lilo, Gustavo A. Rubio, Sharon J. Elliot,