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Modulation of allergic inflammation in the lung by a peptide derived from Mycobacteria tuberculosis chaperonin 60.1.

结核分枝杆菌伴侣蛋白 60.1 衍生的肽对肺部过敏性炎症的调节。

  • 影响因子:4.19
  • DOI:10.1111/cea.13550
  • 作者列表:"Riffo-Vasquez Y","Kanabar V","Keir SD","E-Lacerda RR","Man F","Jackson DJ","Corrigall V","Coates ARM","Page CP
  • 发表时间:2020-04-01
Abstract

BACKGROUND:We have previously demonstrated that Mycobacteria tuberculosis chaperonin 60.1 inhibits leucocyte diapedesis and bronchial hyperresponsiveness in a murine model of allergic lung inflammation. METHODS:In the present study, we have investigated the effect of a shorter peptide sequence derived from Cpn 60.1, named IRL201104, on allergic lung inflammation induced by ovalbumin (OVA) in mice and by house dust mite (HDM) in guinea pigs, as well as investigating the action of IRL201104 on human cells in vitro. RESULTS:Pre-treatment of mice or guinea pigs with IRL201104 inhibits the infiltration of eosinophils to the lung, cytokine release, and in guinea pig skin, inhibits allergen-induced vascular permeability. The protective effect of intranasal IRL201104 against OVA-induced eosinophilia persisted for up to 20 days post-treatment. Moreover, OVA-sensitized mice treated intranasally with 20 ng/kg of IRL201104 show a significant increase in the expression of the anti-inflammatory molecule ubiquitin A20 and significant inhibition of the activation of NF-κB in lung tissue. Our results also show that A20 expression was significantly reduced in blood leucocytes and ASM obtained from patients with asthma compared to cells obtained from healthy subjects which were restored after incubation with IRL201104 in vitro, when added alone, or in combination with LPS or TNF-α in ASM. CONCLUSIONS:Our results suggest that a peptide derived from mycobacterial Cpn60.1 has a long-lasting anti-inflammatory and immunomodulatory activity which may help explain some of the protective effects of TB against allergic diseases.

摘要

背景: 我们以前已经证明,在过敏性肺部炎症的小鼠模型中,分枝杆菌结核分子伴侣蛋白 60.1 抑制白细胞出汗和支气管高反应性。 方法: 在本研究中,我们研究了来自 Cpn 60.1 的较短肽序列,命名为 IRL201104,对卵清蛋白 (OVA) 诱导的过敏性肺部炎症的影响。小鼠和豚鼠屋尘螨 (HDM),以及研究 IRL201104 在体外对人体细胞的作用。 结果: 用 IRL201104 预处理小鼠或豚鼠可抑制嗜酸性粒细胞对肺的浸润、细胞因子的释放,并在豚鼠皮肤中抑制变应原诱导的血管通透性。鼻内 IRL201104 对 OVA 诱导的嗜酸性粒细胞增多的保护作用在治疗后持续长达 20 天。此外,OVA 致敏小鼠经 20 ng/kg IRL201104 鼻内处理后,抗炎分子泛素 A20 的表达显著增加,肺内 NF-κ b 的活化显著抑制。组织。我们的结果还表明,与健康受试者获得的细胞相比,A20 在哮喘患者获得的血液白细胞和 ASM 中的表达显著降低,后者在体外与 IRL201104 孵育后恢复。单独加入时,或在 ASM 中与 LPS 或 TNF-α 组合。 结论: 我们的结果表明,来源于分枝杆菌 Cpn60.1 的肽具有持久的抗炎和免疫调节活性,这可能有助于解释 TB 对过敏性疾病的一些保护作用。

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