Details

Autor(en) / Beteiligte

• Wang, Gang
• Liu, Chun-Tao
• Wang, Zeng-Li
• Jiang, Li-Li
• Yan, Cun-Liang
• Luo, Feng-Min

Titel

Antisense oligonucleotides-induced local blockade of T-bet expression leads to airway inflammation in rats

Ist Teil von

• Acta pharmacologica Sinica, 2006-05, Vol.27 (5), p.561-567

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2006

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 interferon-γ, （IFN-γ）, intedeukin-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.