@article{APS3606,
author = {Gang Wang and Chun-tao Liu and Zeng-li Wang and Li-li Jiang and Cun-liang Yan and Feng-min Luo},
title = {Antisense oligonucleotides-induced local blockade of T-bet expression leads to airway inflammation in rats},
journal = {Acta Pharmacologica Sinica},
volume = {27},
number = {5},
year = {2016},
keywords = {},
abstract = {Aim: To explore whether local blockade of T-box expressed in T cells (T-bet) expression in the lungs could lead to airway inflammation.
Methods: Twenty-four rats were randomly divided into 4 groups: saline group, ovalbumin (OVA)-sensitized group, nonsense group, and the antisense group. The OVA-sensitized rats were sensitized and challenged with OVA, and the rats in the nonsense and antisense groups were subjected to an aerosol delivery of the nonsense and antisense oligonucleotides (AS-ODN) of T-bet (0.1%,w/v). The levels of inter-feron-γ (IFN-γ), interleukin-4 (IL-4), and IL-5 in the bronchoalveolar lavage fluid (BALF) were detected by ELISA, and the mRNA and the protein expression of T-bet and GATA-3 genes were examined by in situ hybridization and Western blot analysis, respectively.
Results: The expression of T-bet mRNA and protein in the lungs of the rats in the antisense group were inhibited effectively. The lungs of the rats in the antisense and OVA-sensitized groups showed eosinophil and lymphocyte inflammatory infiltration, and eosinophilia located predominantly around the airways. The number of GATA-3 mRNA-positive cells and the level of GATA-3 protein in the lungs of the rats in the antisense and the OVA-sensitized groups significantly increased. The level of IL-4 and IL-5 in the BALF in the antisense and OVA-sensitized groups were elevated, but the level of IFN-γ decreased markedly.
Conclusion: Antisense ODN-induced local blockade of T-bet expression leads to airway inflammation with a selective alteration in patterns of cytokine expression and recruitment of eosinophil cells similar to that in the OVA-sensitized animals.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/3606}
}