Estrogen receptor beta: expression profile and possible anti-inflammatory role in disease.

J Pharmacol Exp Ther

Respiratory Pharmacology, Airways Diseases, Imperial College London, Faculty of Medicine, National Heart and Lung Institute, London, United Kingdom.

Published: July 2008

AI Article Synopsis

  • * Researchers used human and rodent tissue to assess the expression of ERbeta and its effect on inflammation in asthma-related cells and in vivo models.
  • * Despite showing some receptor activation, the ERbeta agonist tested did not alter the inflammatory response in asthma, suggesting it may not be effective for asthma treatment in clinical settings.

Article Abstract

Estrogen receptor (ER) beta agonists have been demonstrated to possess anti-inflammatory properties in inflammatory disease models. The objective of this study was to determine whether ERbeta agonists affect in vitro and in vivo preclinical models of asthma. mRNA expression assays were validated in human and rodent tissue panels. These assays were then used to measure expression in human cells and our characterized rat model of allergic asthma. ERB-041 [7-ethenyl-2-(3-fluoro-4-hydroxyphenyl)-1,3-benzoxazol-5-ol], an ERbeta agonist, was profiled on cytokine release from interleukin-1beta-stimulated human airway smooth muscle (HASM) cells and in the rodent asthma model. Although ERbeta expression was demonstrated at the gene and protein level in HASM cells, the agonist failed to have an impact on the inflammatory response. Similarly, in vivo, we observed temporal modulation of ERbeta expression after antigen challenge. However, the agonist failed to have an impact on the model endpoints such as airway inflammation, even though plasma levels reflected linear compound exposure and was associated with an increase in receptor activation after drug administration. In these modeling systems of airway inflammation, an ERbeta agonist was ineffective. Although ERbeta agonists are anti-inflammatory in certain models, this novel study would suggest that they would not be clinically useful in the treatment of asthma.

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http://dx.doi.org/10.1124/jpet.108.136275DOI Listing

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