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

• Published in: Acta pharmacologica Sinica Vol. 27; no. 5; pp. 561 - 567
• Main Authors: Wang, Gang, Liu, Chun-Tao, Wang, Zeng-Li, Jiang, Li-Li, Yan, Cun-Liang, Luo, Feng-Min
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.05.2006
• Subjects: Animals; Bronchoalveolar Lavage Fluid - chemistry; Female; GATA3 Transcription Factor - biosynthesis; GATA3 Transcription Factor - genetics; Interferon-gamma - metabolism; Interleukin-4 - metabolism; Interleukin-5 - metabolism; Lung - metabolism; Lung - pathology; Oligonucleotides, Antisense - pharmacology; Ovalbumin - immunology; Pneumonia - metabolism; Pneumonia - pathology; Random Allocation; Rats; Rats, Wistar; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; T-Box Domain Proteins - biosynthesis; T-Box Domain Proteins - genetics; 基因表达; 寡核苷酸; 干扰素; 炎症
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1111/j.1745-7254.2006.00323.x

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.