title: Beneficial effects of ursodeoxycholic acid via inhibition of airway remodelling, apoptosis of airway epithelial cells, and Th2 immune response in murine model of chronic asthma.
abstract: OBJECTIVE
  In previous studies, anti-inflammatory, anti-apoptotic and immunomodulatory effects of ursodeoxycholic acid (UDCA) on liver diseases have been shown. In this study, we aimed to investigate the effects of UDCA on airway remodelling, epithelial apoptosis, and T Helper (Th)-2 derived cytokine levels in a murine model of chronic asthma.
  
  
  METHODS
  Twenty-seven BALB/c mice were divided into five groups; PBS-Control, OVA-Placebo, OVA-50mg/kg UDCA, OVA-150mg/kg UDCA, OVA-Dexamethasone. Mice in groups OVA-50mg/kg UDCA, OVA-150mg/kg UDCA, OVA-Dexamethasone received the UDCA (50mg/kg), UDCA (150mg/kg), and dexamethasone, respectively. Epithelium thickness, sub-epithelial smooth muscle thickness, number of mast and goblet cells of samples isolated from the lung were measured. Immunohistochemical scorings of the lung tissue for matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEG-F), transforming growth factor-beta (TGF-β), terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) and cysteine-dependent aspartate-specific proteases (caspase)-3 were determined. IL-4, IL-5, IL-13, Nitric oxide, ovalbumin-specific immunoglobulin (Ig) E levels were quantified.
  
  
  RESULTS
  The dose of 150mg/kg UDCA treatment led to lower epithelial thickness, sub-epithelial smooth muscle thickness, goblet and mast cell numbers compared to placebo. Except for MMP-9 and TUNEL all immunohistochemical scores were similar in both UDCA treated groups and the placebo. All cytokine levels were significantly lower in group IV compared to the placebo.
  
  
  CONCLUSIONS
  These findings suggested that the dose of 150mg/kg UDCA improved all histopathological changes of airway remodelling and its beneficial effects might be related to modulating Th-2 derived cytokines and the inhibition of apoptosis of airway epithelial cells.
authors.affiliation: Dokuz Eylul University, Department of Pediatric Allergy and Immunology, Izmir, Turkey. Electronic address: drsakinekar83@hotmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Işık
authors.affiliation: Dokuz Eylul University, Department of Microbiology, Izmir, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Karaman
authors.affiliation: Dokuz Eylul University, Department of Histology, Izmir, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Çilaker Micili
authors.affiliation: Dokuz Eylul University, Department of Pediatric Allergy and Immunology, Izmir, Turkey.
authors.forename: Ş
authors.initials: Ş
authors.lastname: Çağlayan-Sözmen
authors.affiliation: Dokuz Eylul University, Department of Histology, Izmir, Turkey.
authors.forename: H Alper
authors.initials: HA
authors.lastname: Bağrıyanık
authors.affiliation: Dokuz Eylul University, Department of Pediatric Allergy and Immunology, Izmir, Turkey.
authors.forename: Z
authors.initials: Z
authors.lastname: Arıkan-Ayyıldız
authors.affiliation: Dokuz Eylul University, Department of Pediatric Allergy and Immunology, Izmir, Turkey.
authors.forename: N
authors.initials: N
authors.lastname: Uzuner
authors.affiliation: Dokuz Eylul University, Department of Pediatric Allergy and Immunology, Izmir, Turkey.
authors.forename: Ö
authors.initials: Ö
authors.lastname: Karaman
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D014580:Ursodeoxycholic Acid; D020780:Matrix Metalloproteinase 9
keywords: Airway remodelling; Apoptosis; Asthma; Murine model; Th2; Ursodeoxycholic acid