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白细胞介素-36 受体拮抗剂通过抑制白细胞介素-36 通路的激活缓解哮喘中的气道炎症。

Interleukin-36 receptor antagonist alleviates airway inflammation in asthma via inhibiting the activation of Interleukin-36 pathway.

机构信息

Department of Pediatrics, First Peoples Hospital of Shangqiu City, Shangqiu 476000, Henan, PR China.

Department of Chinese Medicine, Children Hospital of Kaifeng, Kaifeng 475000, Henan, PR China.

出版信息

Int Immunopharmacol. 2020 Apr;81:106200. doi: 10.1016/j.intimp.2020.106200. Epub 2020 Feb 7.

DOI:10.1016/j.intimp.2020.106200
PMID:32044656
Abstract

BACKGROUNDS

Asthma is characterized as an inflammatory disorder in the respiratory system with increasing tendency. Most of the asthma patients suffered from the disease since childhood. Thus, developing novel therapeutic targets of pediatric asthma is necessary. Here, we conducted the present study to investigate the effects of IL-36RN (Interleukin-36 receptor antagonist), a newly identified anti-inflammatory factor, on asthma.

METHODS

Sixty asthmatic children (30 moderate and 30 mild) were recruited. The levels of IL-36RN in peripheral blood mononuclear cells (PBMCs), serum and induced sputum (IS) samples from asthma patients and healthy controls (HCs) were measured by qPCR and ELISA. The anti-inflammatory effects of IL-36RN were determined in vitro and potential therapeutic effect on asthma was evaluated in the mouse model of asthma.

RESULTS

The mRNA and protein levels of IL-36RN were significant down-regulated in asthmatics than HCs. The IL-36RN significantly suppressed the expression of pro-inflammatory factors in PBMCs and sputum cells from asthma patients in vitro. And delivering IL-36RN into the mouse model of asthma showed disease alleviation. Pathway analysis showed that the IL-36RN may alleviate airway inflammation in asthma through suppressing the activation of IL-36 pathway.

CONCLUSION

Our data here indicated that IL-36RN may alleviate airway inflammation in asthma through suppressing the activation of IL-36 pathway.

摘要

背景

哮喘是一种以呼吸系统炎症为特征的疾病,且呈上升趋势。大多数哮喘患者从儿童时期就患有这种疾病。因此,有必要开发小儿哮喘的新治疗靶点。在这里,我们进行了本研究,以调查白细胞介素-36 受体拮抗剂(IL-36RN)(一种新发现的抗炎因子)对哮喘的影响。

方法

招募了 60 名哮喘儿童(30 名中度和 30 名轻度)。通过 qPCR 和 ELISA 测量哮喘患者和健康对照者(HCs)外周血单个核细胞(PBMCs)、血清和诱导痰(IS)样本中 IL-36RN 的水平。在体外测定了 IL-36RN 的抗炎作用,并在哮喘小鼠模型中评估了其对哮喘的潜在治疗作用。

结果

哮喘患者的 IL-36RN mRNA 和蛋白水平明显低于 HCs。IL-36RN 可显著抑制哮喘患者 PBMCs 和痰液细胞中促炎因子的表达。将 IL-36RN 递送至哮喘小鼠模型中可减轻疾病。通路分析表明,IL-36RN 可能通过抑制 IL-36 通路的激活来减轻哮喘中的气道炎症。

结论

我们的数据表明,IL-36RN 可能通过抑制 IL-36 通路的激活来减轻哮喘中的气道炎症。

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