Morphologic Damage of Rat Alveolar Epithelial Type II Cells Induced by Bile Acids Could Be Ameliorated by Farnesoid X Receptor Inhibitor Z-Guggulsterone In Vitro

Biomed Res Int. 2016:2016:9283204. doi: 10.1155/2016/9283204. Epub 2016 Jun 1.

Abstract

Objective. To determine whether bile acids (BAs) affect respiratory functions through the farnesoid X receptor (FXR) expressed in the lungs and to explore the possible mechanisms of BAs-induced respiratory disorder. Methods. Primary cultured alveolar epithelial type II cells (AECIIs) of rat were treated with different concentrations of chenodeoxycholic acid (CDCA) in the presence or absence of FXR inhibitor Z-guggulsterone (GS). Then, expression of FXR in nuclei of AECIIs was assessed by immunofluorescence microscopy. And ultrastructural changes of the cells were observed under transmission electron microscope and analyzed by Image-Pro Plus software. Results. Morphologic damage of AECIIs was exhibited in high BAs group in vitro, with high-level expression of FXR, while FXR inhibitor GS could attenuate the cytotoxicity of BAs to AECIIs. Conclusions. FXR expression was related to the morphologic damage of AECIIs induced by BAs, thus influencing respiratory functions.

MeSH terms

  • Alveolar Epithelial Cells / drug effects
  • Alveolar Epithelial Cells / metabolism
  • Alveolar Epithelial Cells / pathology*
  • Alveolar Epithelial Cells / ultrastructure
  • Animals
  • Cell Shape / drug effects*
  • Cells, Cultured
  • Chenodeoxycholic Acid / toxicity*
  • Cytoplasm / drug effects
  • Cytoplasm / metabolism
  • Fluorescent Antibody Technique
  • Male
  • Pregnenediones / pharmacology*
  • Rats, Sprague-Dawley
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors*
  • Receptors, Cytoplasmic and Nuclear / metabolism

Substances

  • Pregnenediones
  • Receptors, Cytoplasmic and Nuclear
  • farnesoid X-activated receptor
  • Chenodeoxycholic Acid
  • pregna-4,17-diene-3,16-dione