Attenuated airways inflammation and remodeling in IL-37a and IL-37b transgenic mice with an ovalbumin-induced chronic asthma

IF 3.7 4区 医学 Q2 CELL BIOLOGY
Lele Cui , Xiaofeng Qin , Tingting Fu , Chenduo Li , Dan Wang , Yue Hu , Yan Li , Yan Chen , Ye Cui , Jingjing Wang , Huihui Yuan , Zhe Lv , Jie Liu , Damo Xu , Rongfei Wei , Sun Ying , Wei Wang
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引用次数: 0

Abstract

Background

Asthma is a common chronic respiratory disease characterized by airways inflammation, hyperresponsiveness and remodeling. IL-37, an anti-inflammatory cytokine, consists of five splice isoforms, that is, a-e. Although it has been previously shown that recombinant human IL-37b is able to inhibit airway inflammation and hyperresponsiveness in animal models of asthma, the effects and difference of other IL-37 isoforms, such as IL-37a on features of asthma are unknown.

Methods

Animal models of chronic asthma were established using IL-37a and IL-37b transgenic mice with C57BL/6J background and wild-type (WT) mice sensitized and nasally challenged with ovalbumin (OVA). Airway hyperresponsiveness was measured using FlexiVent apparatus, while histological and immunohistological stainings were employed to measure airways inflammation and remodeling indexes, including goblet cell metaplasia, mucus production, deposition of collagen, hypertrophy of airway smooth muscles and pulmonary angiogenesis.

Results

Compared to WT mice, both IL-37a and IL-37b transgenic mice had significant reduced airway hyperresponsiveness and the declined total numbers of inflammatory cells, predominant eosinophils into airways and lung tissues. Furthermore, all features of airways remodeling, including degrees of mucus expression, collagen deposition, hypertrophy of smooth muscles, thickness of airways and neovascularization markedly decreased in IL-37 transgenic mice compared with OVA-treated WT mice.

Conclusion

Our data suggest that both IL-37a and IL-37b isoforms are able to not only ameliorate airways inflammation and airways hyperresponsiveness, but also greatly reduce airways structural changes of animal models of chronic asthma.

IL-37a和IL-37b转基因小鼠卵清蛋白诱导的慢性哮喘气道炎症和重塑
背景哮喘是一种常见的慢性呼吸道疾病,以气道炎症、高反应性和重塑为特征。IL-37是一种抗炎细胞因子,由五种剪接异构体组成,即a-e。尽管先前已经表明重组人IL-37b能够在哮喘动物模型中抑制气道炎症和高反应性,但其他IL-37亚型(如IL-37a)对哮喘特征的影响和差异尚不清楚。方法采用C57BL/6J背景的IL-37a和IL-37b转基因小鼠和卵清蛋白(OVA)致敏和鼻激发的野生型(WT)小鼠建立慢性哮喘动物模型。使用FlexiVent设备测量气道高反应性,同时使用组织学和免疫组织学染色来测量气道炎症和重塑指数,包括杯状细胞化生、粘液产生、胶原沉积、气道平滑肌肥大和肺血管生成。结果与野生型小鼠相比,IL-37a和IL-37b转基因小鼠的气道高反应性显著降低,炎症细胞总数下降,主要是进入气道和肺组织的嗜酸性粒细胞。此外,与OVA处理的WT小鼠相比,IL-37转基因小鼠的气道重塑的所有特征,包括粘液表达程度、胶原沉积、平滑肌肥大、气道厚度和新生血管形成,都显著降低。结论IL-37a和IL-37b亚型均能改善慢性哮喘动物模型的气道炎症和气道高反应性,并能显著减少气道结构变化。
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来源期刊
Cellular immunology
Cellular immunology 生物-免疫学
CiteScore
8.20
自引率
2.30%
发文量
102
审稿时长
30 days
期刊介绍: Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered. Research Areas include: • Antigen receptor sites • Autoimmunity • Delayed-type hypersensitivity or cellular immunity • Immunologic deficiency states and their reconstitution • Immunologic surveillance and tumor immunity • Immunomodulation • Immunotherapy • Lymphokines and cytokines • Nonantibody immunity • Parasite immunology • Resistance to intracellular microbial and viral infection • Thymus and lymphocyte immunobiology • Transplantation immunology • Tumor immunity.
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