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在变应性鼻炎动物模型中,CpG基序寡脱氧核苷酸-屋尘螨缀合物对变应性反应的抑制作用

Suppression of allergic response by CpG motif oligodeoxynucleotide-house-dust mite conjugate in animal model of allergic rhinitis.

作者信息

Mo Ji-Hun, Park Seok-Won, Rhee Chae-Seo, Takabayashi Kenji, Lee Seung Sin, Quan Song-Hua, Kim In-Sang, Min Il Yang-Gi, Raz Eyal, Lee Chul Hee

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, Korea.

出版信息

Am J Rhinol. 2006 Mar-Apr;20(2):212-8.

Abstract

BACKGROUND

Although there have been many therapeutic options for allergic disease, the true allergen desensitization remains a challenging goal. The classic immunotherapy has a limited efficacy, is inconvenient, and has a risk of anaphylaxis. Recent reports revealed that immunostimulatory DNA sequences (ISS-oligdeoxynucleotide [ODN], CpG motif) act as a strong Th1 response-inducing adjuvants and that DNA-based vaccination might be an effective therapeutic option. In this study, we investigate whether ISS-ODN/Dermatophagoides farinae (Der f) conjugate has antiallergic effects in the allergic rhinitis mouse model, sensitive to house-dust mites. Der f is the most common allergen-inducing allergic rhinitis in Korea.

METHODS

C57BL/6 mice were sensitized with crude extract of Der f. After injection of ISS-ODN or ISS-ODN/Der f conjugate, several parameters of allergic response were evaluated.

RESULTS

Scratching and sneezing symptoms and eosinophilic infiltration into nasal mucosa were suppressed by injection with ISS-ODN only and ISS-ODN/Der f conjugate. Interleukin-5 level was decreased and interferon gamma level was increased in nasal lavage fluid by injection of ISS-ODN/Der f conjugate. Der f-specific immunoglobulin E was decreased by injection of ISS-ODN or Der f /ISS-ODN conjugate; however, these were not statistically significant. Transforming growth factor beta1 secreted by cultured splenocyte was increased significantly in ISS-ODN/Der f conjugate group.

CONCLUSION

These results suggest ISS-ODN/Der f conjugate induces an antiallergic effect and induces an increase in transforming growth factor beta1 level in the allergic rhinitis model using Der f allergen. Allergic response developed by Der f allergen could be more effectively reduced by injection with ISS-ODN/Der f conjugate than by injection with ISS-ODN only.

摘要

背景

尽管针对过敏性疾病已有多种治疗选择,但真正的过敏原脱敏仍是一个具有挑战性的目标。经典免疫疗法疗效有限、使用不便且有过敏反应风险。最近的报告显示,免疫刺激DNA序列(ISS - 寡脱氧核苷酸[ODN],CpG基序)可作为诱导强烈Th1反应的佐剂,基于DNA的疫苗接种可能是一种有效的治疗选择。在本研究中,我们调查了ISS - ODN/粉尘螨(Der f)缀合物在对屋尘螨敏感的变应性鼻炎小鼠模型中是否具有抗过敏作用。Der f是韩国引起变应性鼻炎最常见的过敏原。

方法

用Der f粗提物致敏C57BL/6小鼠。注射ISS - ODN或ISS - ODN/Der f缀合物后,评估过敏反应的几个参数。

结果

仅注射ISS - ODN和注射ISS - ODN/Der f缀合物均可抑制搔抓和打喷嚏症状以及嗜酸性粒细胞向鼻黏膜的浸润。注射ISS - ODN/Der f缀合物后,鼻灌洗液中白细胞介素 - 5水平降低,干扰素γ水平升高。注射ISS - ODN或Der f /ISS - ODN缀合物后,Der f特异性免疫球蛋白E降低;然而,这些差异无统计学意义。在ISS - ODN/Der f缀合物组中,培养的脾细胞分泌的转化生长因子β1显著增加。

结论

这些结果表明,ISS - ODN/Der f缀合物在使用Der f过敏原的变应性鼻炎模型中诱导了抗过敏作用,并诱导转化生长因子β1水平升高。与仅注射ISS - ODN相比,注射ISS - ODN/Der f缀合物能更有效地减轻Der f过敏原引发的过敏反应。

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