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Environmental Tobacco Smoke and Progesterone Alter Lung Inflammation and Mucous Metaplasia in a Mouse Model of Allergic Airway Disease

  • Valerie L. Mitchell
  • Laura S. Van Winkle
  • Laurel J. Gershwin
Article

Abstract

The prevalence and severity of asthma is sexually dimorphic. Adult women have a higher incidence of asthma than men. This suggests that this disease may have a hormonal component. Progesterone has been shown to elicit an immune response similar to that seen in allergic asthma and previous studies have shown that progesterone increases total IgE levels in the peripheral blood. In the current study, we examine the effect of environmental tobacco smoke (ETS) and progesterone on hallmarks of asthma pathology in lung tissue with the goal of defining whether progesterone can also exacerbate two key features of airway remodeling: accumulation of eosinophils and increased mucous. We used a mouse model of allergic asthma that includes house dust mite allergen (HDMA). Adult female BALB/c mice were ovariectomized and implanted with time-release progesterone pellets. Mice were housed in filtered air or ETS for 6 weeks (1 mg/m3 total suspended particulate) and exposed to HDMA by inhalation. Progesterone alone did not increase mucous cell mass or the abundance of eosinophils but ETS coupled with progesterone exposure resulted in a significant increase in mucous cell metaplasia and increased accumulation of eosinophils in the asthma model. Levels of cytokines in the bronchoalveolar lavage fluid, measured using a multiplex cytokine assay, revealed elevated levels of both interleukin (IL)-5 and IL-12(p40) in HDMA-exposed animals. The addition of progesterone further exacerbated this response. We conclude that progesterone, in the absence of estrogen, exacerbates airway inflammation and airway remodeling induced by the toxicant ETS.

Keywords

Environmental tobacco smoke Mouse model of asthma Progesterone 

Notes

Acknowledgments

The authors thank Brian Tarkington, Imelda Espiritu, Marie Suffia, Tammi Harrington, Trenton Combs, and Jackie Chan for their technical expertise as well as Dr. Neil Willits for statistical consultation.

Funding

Funding was provided by the California Tobacco-Related Disease Research Program of the University of California, Grant Number 14IT-0081 (to LG), NIH RO1 ES012720 and FAMRI (to LV), and NHBLI #T32 HL007013 (to VM).

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Valerie L. Mitchell
    • 1
    • 2
  • Laura S. Van Winkle
    • 2
    • 3
  • Laurel J. Gershwin
    • 1
  1. 1.School of Veterinary Medicine, Department of Pathology, Microbiology, and ImmunologyUniversity of California, DavisDavisUSA
  2. 2.Center for Health and the EnvironmentUniversity of California, DavisDavisUSA
  3. 3.School of Veterinary Medicine, Department of Anatomy, Physiology, and Cell BiologyUniversity of California, DavisDavisUSA

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