Please cite this article in press as: Is ¸ık S, et al. 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. Allergol
Immunopathol (Madr). 2017. http://dx.doi.org/10.1016/j.aller.2016.12.003
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Allergol Immunopathol (Madr). 2017;xxx(xx):xxx---xxx
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Allergologia et
immunopathologia
Sociedad Espa ˜ nola de Inmunolog´ ıa Cl´ ınica,
Alergolog´ ıa y Asma Pedi ´ atrica
ORIGINAL ARTICLE
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
S. Is ¸ık
a,*
, M. Karaman
b
, S. C ¸ilaker Micili
c
, S ¸. C ¸a˘ glayan-Sözmen
a
, H. Alper Ba˘ grıyanık
c
,
Z. Arıkan-Ayyıldız
a
, N. Uzuner
a
, Ö. Karaman
a
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
Received 26 August 2016; accepted 3 December 2016
KEYWORDS
Asthma;
Airway remodelling;
Apoptosis;
Ursodeoxycholic acid;
Murine model;
Th2
Abstract
Background and aims: In previous studies, anti-inflammatory, anti-apoptotic and immunomod-
ulatory 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-50 mg/kg UDCA, OVA-150 mg/kg UDCA, OVA-Dexamethasone. Mice in groups OVA-50 mg/kg
UDCA, OVA-150 mg/kg UDCA, OVA-Dexamethasone received the UDCA (50 mg/kg), UDCA
(150 mg/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-),
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 150 mg/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.
∗
Corresponding author.
E-mail address: drsakinekar83@hotmail.com (S. Is ¸ık).
http://dx.doi.org/10.1016/j.aller.2016.12.003
0301-0546/© 2017 SEICAP. Published by Elsevier Espa˜ na, S.L.U. All rights reserved.