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Asthma-like airway inflammation and responses in a rat model of atopic dermatitis induced by neonatal capsaicin treatment

Authors Han RT, Kim S, Choi K, Jwa H, Lee J, Kim HY, Kim HJ, Kim HR, Back SK, Na HS

Received 17 October 2016

Accepted for publication 6 February 2017

Published 18 May 2017 Volume 2017:10 Pages 181—189

DOI https://doi.org/10.2147/JAA.S124902

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Amrita Dosanjh

Supplementary video of the scratching behaviors in Sprague Dawley rats

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Rafael Taeho Han,1,2 Sewon Kim,3 Kyungmin Choi,1,2 Hyeonseok Jwa,1,2 JaeHee Lee,1,2 Hye Young Kim,1,2 Hee Jin Kim,4 Hang-Rae Kim,5 Seung Keun Back,6 Heung Sik Na1,2

1Neuroscience Research Institute, 2Department of Physiology, 3Department of Microbiology, College of Medicine, Korea University, Seoul, 4Division of Biological Science and Technology, Science and Technology College, Yonsei University Wonju Campus, Wonju, 5Department of Anatomy, College of Medicine, Seoul National University, Seoul, 6Department of Pharmaceutics and Biotechnology, College of Medical Engineering, Konyang University, Chungnam, South Korea

Abstract: Recent studies have shown that approximately 70% of patients with severe atopic dermatitis (AD) develop asthma. Development of AD in infancy and subsequent other atopic diseases such as asthma in childhood is referred to as atopic march. However, a causal link between the diseases of atopic march has remained largely unaddressed, possibly due to lack of a proper animal model. Recently, we developed an AD rat model showing chronically relapsing dermatitis and scratching behaviors induced by neonatal capsaicin treatment. Here, we investigated whether our model also showed asthmatic changes, with the aim of expanding our AD model into an atopic march model. First, we confirmed that capsaicin treatment (50 mg/kg within 24 h after birth) induced dermatitis and scratching behaviors until 6 weeks of age. After that, the mRNA expression of Th1 and Th2 cytokines, such as IFN-γ and TNF-α, and IL-4, IL-5, and IL-13, respectively, was quantified with quantitative real-time polymerase chain reaction in the skin and the lungs. The number of total cells and eosinophils was counted in bronchoalveolar lavage (BAL) fluid. The levels of IgE in the serum and BAL fluid were determined with enzyme-linked immunosorbent assay. Paraffin-embedded sections (4 μm) were stained with hematoxylin/eosin to analyze the morphology of the lung and the airway. Airway responsiveness was measured in terms of airway resistance and compliance using the flexiVent system. In the capsaicin-treated rats, persistent dermatitis developed, and scratching behaviors increased over several weeks. The levels of IgE in the serum and BAL fluid as well as the mRNA expression of Th2 cytokines, including IL-4, IL-5, and IL-13, in both the skin and the lungs were elevated, and the number of eosinophils in the BAL fluid was also increased in the capsaicin-treated rats compared to control rats. Morphological analysis of the airway revealed smooth muscle hypertrophy and extensive mucus plug in the capsaicin-treated rats. Functional studies demonstrated an increment of the airway resistance and a decrement of lung compliance in the capsaicin-treated rats compared to control rats. Taken together, our findings suggested that neonatal capsaicin treatment induced asthma-like airway inflammation and responses in juvenile rats.

Keywords: atopic march, scratching, cytokines, eosinophils, BAL fluid, pruritus, flexiVent, airway hypertrophy and remodelling
 

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