| 17Beta-estradiol inhibits IL-8 in cystic fibrosis by up-regulating secretory leucoprotease inhibitor. | |
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MedLine Citation:
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PMID: 20378727 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RATIONALE: An unexplained gender gap is observed in cystic fibrosis (CF). Females have poorer lung function, decreased survival, and earlier Pseudomonas colonization. OBJECTIVES: To evaluate the effect of 17beta-estradiol (E(2)) on CF bronchial epithelial cells in vitro and in vivo. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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. |
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Authors:
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Sanjay H Chotirmall; Catherine M Greene; Irene K Oglesby; Warren Thomas; Shane J O'Neill; Brian J Harvey; Noel G McElvaney |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-08 |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: 182 ISSN: 1535-4970 ISO Abbreviation: Am. J. Respir. Crit. Care Med. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-05 Completed Date: 2010-08-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 62-72 Citation Subset: AIM; IM |
Affiliation:
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Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Cells, Cultured Cystic Fibrosis / metabolism* Epithelial Cells / metabolism* Estradiol / physiology* Estrogen Receptor beta / physiology Female Humans Interleukin-8 / metabolism* Male NF-kappa B / physiology Respiratory Mucosa / metabolism Secretory Leukocyte Peptidase Inhibitor / metabolism* Sex Factors Up-Regulation Young Adult |
| Chemical | |
Reg. No./Substance:
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0/Estrogen Receptor beta; 0/IL8 protein, human; 0/Interleukin-8; 0/NF-kappa B; 0/Secretory Leukocyte Peptidase Inhibitor; 50-28-2/Estradiol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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