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Inicio Allergologia et Immunopathologia Beneficial effects of ursodeoxycholic acid via inhibition of airway remodelling,...
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Vol. 45. Issue 4.
Pages 339-349 (July - August 2017)
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Vol. 45. Issue 4.
Pages 339-349 (July - August 2017)
Original Article
DOI: 10.1016/j.aller.2016.12.003
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
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S. Işıka,
Corresponding author
drsakinekar83@hotmail.com

Corresponding author.
, M. Karamanb, S. Çilaker Micilic, Ş. Çağlayan-Sözmena, H. Alper Bağrıyanıkc, Z. Arıkan-Ayyıldıza, N. Uzunera, Ö. Karamana
a Dokuz Eylul University, Department of Pediatric Allergy and Immunology, Izmir, Turkey
b Dokuz Eylul University, Department of Microbiology, Izmir, Turkey
c Dokuz Eylul University, Department of Histology, Izmir, Turkey
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Tables (4)
Table 1. Comparison of the histopathological findings of study groups (mean±SD).
Table 2. Comparison of the immunohistochemical scorings of study groups (mean±SD).
Table 3. Comparison of the cytokine levels in lung homogenates and OVA-specific IgE in serum samples (mean±SD).
Table 4. Comparison of eosinophil counts in BAL fluid (mean±SD).
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Abstract
Background and aims

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.

Keywords:
Asthma
Airway remodelling
Apoptosis
Ursodeoxycholic acid
Murine model
Th2

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