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

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:azhan
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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-fourrats were randomly divided into 4 groups:saline group,ovalbumin (OVA)-sensi-tized group,nonsense group,and the antisense group.The OVA-sensitized ratswere sensitized and challenged with OVA,and the rats in the nonsense andantisense groups were subjected to an aerosol delivery of the nonsense andantisense 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 ofT-bet and GATA-3 genes were examined by in situ hybridization and Western blotanalysis,respectively.Results:The expression of T-bet mRNA and protein in thelungs of the rats in the antisense group were inhibited effectively.The lungs ofthe rats in the antisense and OVA-sensitized groups showed eosinophil and lym-phocyte inflammatory infiltration,and eosinophilia located predominantly aroundthe airways.The number of GATA-3 mRNA-positive cells and the level of GATA-3protein in the lungs of the rats in the antisense and the OVA-sensitized groupssignificantly increased.The level of IL-4 and IL-5 in the BALF in the antisenseand OVA-sensitized groups were elevated,but the level of IFN-γ decreasedmarkedly.Conclusion:Antisense ODN-induced local blockade of T-bet expres-sion leads to airway inflammation with a selective alteration in patterns of cytokineexpression and recruitment of eosinophil cells similar to that in the OVA-sensitizedanimals. Aim: To explore whether T-box expressed in T cells (T-bet) expression in the lungs could lead to airway inflammation. Methods: Twenty-fourrats were randomly divided into 4 groups: saline group, ovalbumin (OVA) sensi-tized group, nonsense group, and the antisense group. The OVA-sensitized ratswere sensitized and challenged with OVA, and the rats in the nonsense andantisense groups were subjected to an aerosol delivery of the nonsense andantisense oligonucleotides (AS-ODN) of T 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 lym-phocyte in flammatory 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 group slightly 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. Conlusion: Antisense ODN-induced local blockade of T-bet expres-sion leads to airway inflammation with a selective alteration in patterns of cytokineexpression and recruitment of eosinophil cells similar to that in the OVA-sensitizedanimals.
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