在过敏性哮喘小鼠模型中，阻断白细胞介素-33/ST2可改善气道炎症。

Blockade of IL-33/ST2 ameliorates airway inflammation in a murine model of allergic asthma.

作者信息

Lee Hea Yon, Rhee Chin Kook, Kang Ji Young, Byun Ji Hae, Choi Joon Young, Kim Seung Joon, Kim Young Kyoon, Kwon Soon Suk, Lee Sook Young

机构信息

1Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

出版信息

Exp Lung Res. 2014 Mar;40(2):66-76. doi: 10.3109/01902148.2013.870261. Epub 2014 Jan 21.

DOI:10.3109/01902148.2013.870261

PMID:24446582

Abstract

OBJECTIVE

Interleukin (IL)-33 is involved in the development of lung inflammation by inducing or amplifying Th2 type-mediated responses in various animal models of allergic asthma. The ST2 gene is a member of the IL-1 receptor family, producing a transmembrane form (ST2L) and a soluble secreted form (sST2). sST2 has been shown to block this IL-33/ST2 signaling pathway. This study aimed to investigate whether anti-IL-33 and sST2 reduced airway inflammation in a murine model of asthma.

METHODS

BALB/c mice were sensitized and challenged with ovalbumin (OVA), and the effect of sST2 and anti-IL-33 antibody on airway inflammation and airway hyperresponsiveness (AHR) was evaluated. Furthermore, we measured changes in various cytokines in the bronchoalveolar lavage (BAL) fluid when treated with sST2 or anti-IL-33.

RESULTS

We observed that anti-IL-33 antibody and sST2 exert a negative regulation on OVA-mediated allergic airway inflammation. Both treatments reduced total cell counts and eosinophil counts in BAL fluid and AHR to methacholine. The Th2 cytokines, such as IL-4, IL-5, and IL-13 in BAL fluid were also significantly decreased after both treatments. However, there were no changes in the level of TGF- ß1 and IL-10 after each treatment.

CONCLUSIONS

These results suggest that anti-IL-33 as well as sST2 have therapeutic potential for allergic asthma through inhibition of Th2 cytokine production.

摘要

目的

在各种过敏性哮喘动物模型中，白细胞介素（IL）-33 通过诱导或放大 Th2 型介导的反应参与肺部炎症的发展。ST2 基因是 IL-1 受体家族的成员，可产生跨膜形式（ST2L）和可溶性分泌形式（sST2）。已证明 sST2 可阻断这种 IL-33/ST2 信号通路。本研究旨在探讨抗 IL-33 和 sST2 是否能减轻哮喘小鼠模型中的气道炎症。

方法

用卵清蛋白（OVA）对 BALB/c 小鼠进行致敏和激发，并评估 sST2 和抗 IL-33 抗体对气道炎症和气道高反应性（AHR）的影响。此外，我们测量了用 sST2 或抗 IL-33 处理时支气管肺泡灌洗（BAL）液中各种细胞因子的变化。

结果

我们观察到抗 IL-33 抗体和 sST2 对 OVA 介导的过敏性气道炎症发挥负调节作用。两种处理均降低了 BAL 液中的总细胞计数和嗜酸性粒细胞计数以及对乙酰甲胆碱的 AHR。两种处理后，BAL 液中的 Th2 细胞因子，如 IL-4、IL-5 和 IL-13 也显著降低。然而，每种处理后 TGF-β1 和 IL-10 的水平没有变化。