eISSN: 1644-4124
ISSN: 1426-3912
Central European Journal of Immunology
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4/2013
vol. 38
 
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abstract:

Inhibition of TLR4/TRIF signaling with Dynasore improves Treg/Th17 cell ratio in mice with induced bronchial asthma

Song-Quan Wu
,
Guang-Li Wang
,
Wei Liang
,
Dan-Li Wang
,
Ru-Hui Yang

(Centr Eur J Immunol 2013; 38 (4): 454-460)
DOI: https://doi.org/10.5114/ceji.2013.39761
Online publish date: 2013/12/30
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Toll-like receptor 4 (TLR4) and increases in Th17 cells have been associated with inflammatory response in bronchial asthma. To determine if altered T cell profiles are present in asthma, and whether inhibition of TLR4 signaling can ameliorate inflammation in this disease, we treated mouse models of asthma with the TLR4/TRIF signaling inhibitor Dynasore. Asthma was induced in twenty mice by challenge with ovalbumin (OVA). Mice were equally and randomly divided into an asthma model group (AST) or a Dynasore treatment group (DYN). Ten additional mice were treated with saline to serve as a control group (CT). Bronchoalveolar lavage fluid (BALF) was collected to determine total white and differential cell counts as well as for ELISA to measure secretion levels of cytokines transforming growth factor 1 (TGF-1), interleukin (IL) 10 (anti-inflammatory) and IL-17 (pro-inflammatory). Asthma model group mice had higher total and differential cell counts, higher amounts of TGF-1 and IL-17, lower amounts of IL-10, and a higher expression of TLR4 than CT mice, which indicated inflammation. The ratio of Treg/Th17 cells was also significantly decreased in AST mice (p < 0.05). However, mice with asthma that were treated with Dynasore exhibited improvements in all of these measures compared with AST mice: decreased cell counts, increased IL-10, decreased IL-17 and TGF-1, decreased TLR4 expression, and an increased ratio of Treg/Th17 cells were observed (p < 0.05), indicating that inhibition of TLR4 signaling improved inflammatory markers. Thus, TLR4/TRIF signaling may play an important role in pathogenesis of asthma by promoting an imbalance of Treg/Th17 cells.
keywords:

TLR4/TRIF, asthma, Treg cell, Th17, ovalbumin, Dynasore

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