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芬苯达唑治疗哮喘模型小鼠可减轻过敏性气道炎症和 Th2 细胞因子的产生。

Treatment of mice with fenbendazole attenuates allergic airways inflammation and Th2 cytokine production in a model of asthma.

机构信息

Australian National University, Canberra, Australian Capital Territory, Australia.

出版信息

Immunol Cell Biol. 2009 Nov-Dec;87(8):623-9. doi: 10.1038/icb.2009.47. Epub 2009 Jul 21.

Abstract

Mouse models have provided a significant insight into the role of T-helper (Th) 2 cytokines such as IL-5 and IL-13 in regulating eosinophilia and other key features of asthma. However, the validity of these models can be compromised by inadvertent infection of experimental mouse colonies with pathogens such as oxyurid parasites (pinworms). While the benzimidazole derivative, fenbendazole (FBZ), is commonly used to treat such outbreaks, the effects of FBZ on mouse models of Th2 disease are largely unknown. In this investigation, we show that mice fed FBZ-supplemented food during the in utero and post-weaning period developed attenuated lung eosinophilia, antigen-specific IgG1 and Th2 cytokine responses in a model of asthma. Treatment of the mediastinal lymph node cells from allergic mice with FBZ in vitro attenuated cell proliferation, IL-5 and IL-13 production and expression of the early lymphocyte activation marker, CD69 on CD4(+) T cells and CD19(+) B cells. In addition, eosinophilia and Th2 responses remained attenuated after a 4-week withholding period in allergic mice treated preweaning with FBZ. Thus, FBZ modulates the amplitude of Th2 responses both in vivo and in vitro.

摘要

鼠模型为研究辅助性 T 细胞(Th)2 细胞因子(如 IL-5 和 IL-13)在调节嗜酸性粒细胞增多症和哮喘的其他关键特征方面的作用提供了重要的见解。然而,实验鼠群无意中感染了病原体,如奥耶尔达线虫(蛔虫),会影响这些模型的有效性。苯并咪唑衍生物芬苯达唑(FBZ)常用于治疗此类爆发,但 FBZ 对 Th2 疾病的鼠模型的影响在很大程度上是未知的。在这项研究中,我们表明,在子宫内和断奶后期间用添加 FBZ 的食物喂养的小鼠,在哮喘模型中发展出肺嗜酸性粒细胞减少、抗原特异性 IgG1 和 Th2 细胞因子反应减弱。体外用 FBZ 处理过敏小鼠的纵隔淋巴结细胞,可减弱细胞增殖、IL-5 和 IL-13 的产生以及 CD4(+)T 细胞和 CD19(+)B 细胞上早期淋巴细胞激活标志物 CD69 的表达。此外,在预断奶时用 FBZ 治疗的过敏小鼠中,即使经过 4 周的停药期,嗜酸性粒细胞增多和 Th2 反应仍然减弱。因此,FBZ 可调节体内和体外 Th2 反应的幅度。

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