Journal
ENDOCRINOLOGY
Volume 151, Issue 1, Pages 174-184Publisher
OXFORD UNIV PRESS INC
DOI: 10.1210/en.2009-0876
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Funding
- European Commission [LSHM-CT-2005-518245]
- National Institutes of Health [MADRI RO1-AG027713-01]
- Italian Ministry of Research [PRIN 20006065483_003]
- NATIONAL INSTITUTE ON AGING [R01AG027713] Funding Source: NIH RePORTER
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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-alpha and/or ER beta, mediates hormone antiinflammatory effects in lung and how gender or aging modify this effect. Acute lung inflammation in wild type, ER alpha or ER beta knockout animals was induced by pleural injection of carrageenan; female mice were used and sham operated, ovariectomized, or ovariectomized and treated with 17 beta-estradiol (E-2) before carrageenan. Our data show that ER alpha, and not ER beta, mediates E-2-induced reduction of the inflammatory response. By real-time PCR and immunohistochemistry assays, we demonstrate ER alpha expression in the resident and infiltrated inflammatory cells of the lung, in which ER beta could not be detected. In these cells, E-2-mediated reduction in the expression of inflammatory mediators was also due to ER alpha. 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 E-2 was similar in the two sexes. Interestingly, aging results in a strong increase in the inflammatory response in both sexes and in the disruption E-2/ER alpha signaling pathway. In conclusion, our data reveal that E-2 is able to regulate lung inflammation in a gender-unrelated, age-restricted manner. The specific involvement of ER alpha in hormone action opens new ways to identify drug targets that limit the inflammatory component of lung pathologies. (Endocrinology 151: 174-184, 2010)
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