Estrogen receptor-α as a drug target candidate for preventing lung inflammation

Elisabetta Vegeto, Salvatore Cuzzocrea, Concetta Crisafulli, Emanuela Mazzon, Angelo Sala, Andreè Krust, Adriana Maggi

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Abstract

Accumulating evidence shows that estrogens are protective factors in inflammatory lung diseases and are involved in the gender-related incidence of these pathologies. The aim of this study was to identify which estrogen receptor (ER), ER-α and/or ERβ, mediates hormone antiinflammatory effects in lung and how gender or aging modify this effect. Acute lung inflammation in wild type, ERα or ERβ knockout animals was induced by pleural injection of carrageenan; female mice were used and sham operated, ovariectomized, or ovariectomized and treated with 17β-estradiol (E2) before carrageenan. Our data show that ERα, and not ERβ, mediates E2-induced reduction of the inflammatory response. By real-time PCR and immunohistochemistry assays, we demonstrate ERα expression in the resident and infiltrated inflammatory cells of the lung, in which ERβ could not be detected. In these cells, E2-mediated reduction in the expression of inflammatory mediators was also due to ERα. In parallel, we observed that female mice were more prone to inflammation as compared with males, suggesting a gender-related difference in lung susceptibility to inflammatory stimuli, whereas the effect of E2 was similar in the two sexes. Interestingly, aging results in a strong increase in the inflammatory response in both sexes and in the disruption E2/ERα signaling pathway. In conclusion, our data reveal that E2 is able to regulate lung inflammation in a gender-unrelated, age-restricted manner. The specific involvement of ERα in hormone action opens new ways to identify drug targets that limit the inflammatory component of lung pathologies.

Original languageEnglish
Pages (from-to)174-184
Number of pages11
JournalEndocrinology
Volume151
Issue number1
DOIs
Publication statusPublished - Jan 2010

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ASJC Scopus subject areas

  • Endocrinology

Cite this

Vegeto, E., Cuzzocrea, S., Crisafulli, C., Mazzon, E., Sala, A., Krust, A., & Maggi, A. (2010). Estrogen receptor-α as a drug target candidate for preventing lung inflammation. Endocrinology, 151(1), 174-184. https://doi.org/10.1210/en.2009-0876