Open AccessAntisense oligonucleotides‐induced local blockade of T‐bet expression leads to airway inflammation in rats 1
Author(s) -
WANG Gang,
LIU Chuntao,
WANG Zengli,
JIANG Lili,
YAN Cunliang,
LUO Fengmin
Publication year - 2006
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00323.x
Subject(s) - ovalbumin , microbiology and biotechnology , inflammation , eosinophil , messenger rna , bronchoalveolar lavage , biology , immunology , chemistry , medicine , immune system , biochemistry , asthma , lung , gene
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.