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在干扰素-β基因敲除小鼠的过敏性气道炎症小鼠模型中使用含CpG基序的局部治疗。

Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-beta knock-out mice.

作者信息

Matheu Victor, Treschow Alexandra, Teige Ingrid, Navikas Vaidrius, Issazadeh-Navikas Shohreh

机构信息

Section of Medical Inflammation Research, Department of Cell & Molecular Biology; Lund University; Sweden.

出版信息

Respir Res. 2005 Mar 5;6(1):25. doi: 10.1186/1465-9921-6-25.

DOI:10.1186/1465-9921-6-25
PMID:15748290
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC555575/
Abstract

BACKGROUND

CpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Furthermore, type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-beta in the immunomodulatory effects of CpG-ODN is not known.

OBJECTIVE

Here, we aimed to elucidate the role of IFN-beta in the anti-allergic effect of CpG motifs.

METHODS

We assessed the immune response in OVA-primed/OVA-challenged IFN-beta knockout (-/-) mice compared to wild type (WT) control, after intranasal and systemic treatment with synthetic CpG motifs.

RESULTS

Vaccination with CpG-ODN reduced the number of cells in airways of OVA-sensitized WT but not IFN-beta-/- mice. Although airway eosinophilia was reduced in both treated groups, they were significantly higher in IFN-beta-/- mice. Other inflammatory cells, such as lymphocytes and macrophages were enhanced in airways by CpG treatment in IFN-beta-/- mice. The ratio of IFN-gamma/IL-4 cytokines in airways was significantly skewed to a Th1 response in WT compared to IFN-beta-/- group. In contrast, IL-4 and IgE were reduced with no differences between groups. Ag-specific T-cell proliferation, Th1-cytokines such as IFN-gamma, IL-2 and also IL-12 were significantly lower in IFN-beta-/- mice. Surprisingly, we discovered that intranasal treatment of mice with CpG-ODN results in mild synovitis particularly in IFN-beta-/- mice.

CONCLUSION

Our results indicate that induction of Th1 response by therapy with CpG-ODN is only slightly and partially dependent on IFN-beta, while IFN-beta is not an absolute requirement for suppression of airway eosinophilia and IgE. Furthermore, our finding of mild synovitis is a warning for possible negative effects of CpG-ODN vaccination.

摘要

背景

CpG寡脱氧核苷酸(CpG-ODN)能够诱导产生大量具有多种免疫调节特性的I型干扰素。此外,I型干扰素被认为在介导CpG-ODN的作用中起关键作用。干扰素-β在CpG-ODN免疫调节作用中的具体作用尚不清楚。

目的

在此,我们旨在阐明干扰素-β在CpG基序抗过敏作用中的作用。

方法

在用合成CpG基序进行鼻内和全身治疗后,我们评估了卵清蛋白致敏的干扰素-β基因敲除(-/-)小鼠与野生型(WT)对照相比的免疫反应。

结果

用CpG-ODN疫苗接种可减少卵清蛋白致敏的WT小鼠气道中的细胞数量,但对干扰素-β-/-小鼠无效。虽然两个治疗组的气道嗜酸性粒细胞增多均有所减少,但在干扰素-β-/-小鼠中显著更高。CpG治疗可使干扰素-β-/-小鼠气道中的其他炎症细胞(如淋巴细胞和巨噬细胞)增多。与干扰素-β-/-组相比,WT小鼠气道中干扰素-γ/白细胞介素-4细胞因子的比例显著偏向于Th1反应。相反,白细胞介素-4和免疫球蛋白E减少,两组之间无差异。在干扰素-β-/-小鼠中,抗原特异性T细胞增殖、Th1细胞因子(如干扰素-γ、白细胞介素-2以及白细胞介素-12)显著降低。令人惊讶的是,我们发现用CpG-ODN对小鼠进行鼻内治疗会导致轻度滑膜炎,尤其是在干扰素-β-/-小鼠中。

结论

我们的结果表明,用CpG-ODN治疗诱导Th1反应仅轻微且部分依赖于干扰素-β,而干扰素-β并非抑制气道嗜酸性粒细胞增多和免疫球蛋白E的绝对必需条件。此外,我们发现的轻度滑膜炎警示了CpG-ODN疫苗接种可能存在的负面影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bde/555575/b75494a5dbb6/1465-9921-6-25-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bde/555575/c472251a8de7/1465-9921-6-25-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bde/555575/1526837f02d0/1465-9921-6-25-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bde/555575/e08d9d9b3e25/1465-9921-6-25-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bde/555575/2a2686760307/1465-9921-6-25-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bde/555575/2c5a2bab0d43/1465-9921-6-25-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bde/555575/b75494a5dbb6/1465-9921-6-25-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bde/555575/c472251a8de7/1465-9921-6-25-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bde/555575/1526837f02d0/1465-9921-6-25-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bde/555575/e08d9d9b3e25/1465-9921-6-25-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bde/555575/2a2686760307/1465-9921-6-25-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bde/555575/2c5a2bab0d43/1465-9921-6-25-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bde/555575/b75494a5dbb6/1465-9921-6-25-6.jpg

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