Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma.

Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma.
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DOI:
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发表时间:
1998
影响因子:
4.4
通讯作者:
J. Kline;T. Waldschmidt;T. Businga;J. E. Lemish;J. Weinstock;P. Thorne;A. Krieg
J. Kline;T. Waldschmidt;T. Businga;J. E. Lemish;J. Weinstock;P. Thorne;A. Krieg
中科院分区:
医学2区
文献类型:
--
作者:
J. Kline;T. Waldschmidt;T. Businga;J. E. Lemish;J. Weinstock;P. Thorne;A. Krieg

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哮喘在工业化国家一直在增加。有证据表明,哮喘是由Th2对吸入环境抗原的免疫反应引起的,而儿童感染可以预防这种免疫反应。我们已经表明,细菌DNA含有基序,集中在未甲基化的CpG二核苷酸,诱导Th1型反应。我们假设这些CpG基序的Th1效应可能对抗Th2型过敏反应,并认为这可能是儿童感染对哮喘的保护作用。我们研究了CpG基序寡脱氧核苷酸(CpG ODN)在小鼠哮喘模型中的作用。联合应用CpG ODN和Ag可预防气道嗜酸性粒细胞增多、Th2细胞因子诱导、IgE产生和支气管高反应性。值得注意的是,在先前致敏的小鼠中,CpG ODN可以预防过敏原诱导的气道炎症。这些研究表明,暴露于CpG DNA可以预防哮喘。
Asthma has been increasing in industrialized countries. Evidence suggests that asthma is caused by a Th2 immune response to inhaled environmental Ags and that childhood infections protect against this. We have shown that bacterial DNA contains motifs, centered on unmethylated CpG dinucleotides, which induce Th1-type responses. We hypothesized that the Th1 effect of these CpG motifs may oppose the Th2 type allergic response and suggest that this may account for the protective effect of childhood infection against asthma. We examined the effects of CpG-motif oligodeoxynucleotides (CpG ODN) in a murine model of asthma. Airway eosinophilia, Th2 cytokine induction, IgE production, and bronchial hyperreactivity were prevented by coadministration of CpG ODN with the Ag. Significantly, in a previously sensitized mouse, CpG ODN can prevent allergen-induced airway inflammation. These studies suggest that exposure to CpG DNA may protect against asthma.