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17Beta-estradiol inhibits IL-8 in cystic fibrosis by up-regulating secretory leucoprotease inhibitor.
- Source :
- American Journal of Respiratory & Critical Care Medicine; 7/1/2010, Vol. 182 Issue 1, p62-72, 11p
- Publication Year :
- 2010
-
Abstract
- <bold>Rationale: </bold>An unexplained gender gap is observed in cystic fibrosis (CF). Females have poorer lung function, decreased survival, and earlier Pseudomonas colonization.<bold>Objectives: </bold>To evaluate the effect of 17beta-estradiol (E(2)) on CF bronchial epithelial cells in vitro and in vivo.<bold>Methods: </bold>On exposure of CFBE41o- cultures to physiological concentrations of E(2), there was a significant dose-dependent inhibition of IL-8 release induced by toll-like receptor agonists, CF bronchoalveolar lavage fluid, or Pseudomonas-conditioned media. Estrogen receptor (ER)-alpha and -beta expression was quantified in cell lines and bronchial brushings from CF and non-CF patients.<bold>Measurements and Main Results: </bold>Both receptors were expressed in vitro and in vivo, although ERbeta expression was significantly higher in CF. Using ER isoform-specific agonists and antagonists, we established that ERbeta mediates the inhibition of CF bronchoalveolar lavage fluid-induced IL-8 release. We also showed that secretory leucoprotease inhibitor gene expression and protein localization to the nucleus increased in response to E(2). Secretory leucoprotease inhibitor knockdown abrogated the inhibitory effects of E(2).<bold>Conclusions: </bold>E(2) inhibits IL-8 release by ERbeta in CF bronchial epithelial cells through up-regulation of secretory leucoprotease inhibitor, inhibition of nuclear factor (NF)-kappaB, and IL-8 gene expression. These data implicate a novel anti-inflammatory mechanism for E(2) in females with CF, which predisposes to infection and colonization. This could, in part, account for the observed gender dichotomy in CF. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1073449X
- Volume :
- 182
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- American Journal of Respiratory & Critical Care Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 105044387
- Full Text :
- https://doi.org/10.1164/rccm.201001-0053OC