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Psoriatic inflammation enhances allergic airway inflammation through IL-23/STAT3 signaling in a murine model

机译:银屑病炎症通过IL-23 / Stat3信号传导在鼠模型中增强过敏气道炎症

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摘要

Psoriasis is an autoimmune inflammatory skin disease characterized by activated IL-23/STAT3/Th17 axis. Recently psoriatic inflammation has been shown to be associated with asthma. However, no study has previously explored how psoriatic inflammation affects airway inflammation. Therefore, this study investigated the effect of imiquimod (IMQ)-induced psoriatic inflammation on cockroach extract (CE)-induced airway inflammation in murine models. Mice were subjected to topical and intranasal administration of IMQ and CE to develop psoriatic and airway inflammation respectively. Various analyses in lung/spleen related to inflammation, Th17/Th2/Th1 cell immune responses, and their signature cytokines/transcription factors were carried out. Psoriatic inflammation in allergic mice was associated with increased airway inflammation with concurrent increase in Th2/Th17 cells/signature cytokines/transcription factors. Splenic CD4+ T and CD11c+ dendritic cells in psoriatic mice had increased STAT3/RORC and IL-23 mRNA expression respectively. This led us to explore the effect of systemic IL-23/STAT3 signaling on airway inflammation. Topical application of STA-21, a small molecule STAT3 inhibitor significantly reduced airway inflammation in allergic mice having psoriatic inflammation. On the other hand, adoptive transfer of IL-23-treated splenic CD4+ T cells from allergic mice into naive recipient mice produced mixed neutrophilic/eosinophilic airway inflammation similar to allergic mice with psoriatic inflammation. Our data suggest that systemic IL-23/STAT3 axis is responsible for enhanced airway inflammation during psoriasis. The current study also suggests that only anti-asthma therapy may not be sufficient to alleviate airway inflammatory burden in asthmatics with psoriasis. (C) 2016 Elsevier Inc. All rights reserved.
机译:牛皮癣是一种自身免疫性炎症性皮肤病,其特征在于活化的IL-23 / Stat3 / Th17轴。最近的银屑病炎症已显示与哮喘有关。然而,先前没有研究过探索了银屑病炎症如何影响气道炎症。因此,本研究研究了咪喹莫德(IMQ)诱导的银屑病对蟑螂提取物(Ce)诱导的鼠模型中的气道炎症的影响。对小鼠进行局部和鼻内给予IMQ和CE,分别开发银屑病和气道炎症。进行了与炎症,Th17 / Th2 / Th1细胞免疫反应相关的肺/脾分析及其签名细胞因子/转录因子。过敏小鼠的银屑病炎症与随着TH2 / TH17细胞/特征细胞因子/转录因子的同时增加的气道炎症增加。银屑病小鼠中的脾CD4 + T和CD11C +树突细胞分别增加了STAT3 / RORC和IL-23 mRNA表达。这使我们探讨了系统IL-23 / Stat3信号对气道炎症的影响。 STA-21的局部应用,小分子Stat3抑制剂显着降低了具有银屑病炎症的过敏小鼠中的气道炎症。另一方面,通过将过敏小鼠的IL-23处理的脾蛋白CD4 + T细胞通过与具有银屑病的过敏小鼠类似的混合中性/嗜酸性气道炎症,通过将IL-23处理的脾脏CD4 + T细胞从过敏小鼠中产生。我们的数据表明,系统性IL-23 / Stat3轴负责牛皮癣期间的增强型气道炎症。目前的研究还表明,只有抗哮喘治疗可能不足以缓解哮喘患者的气道炎症负担。 (c)2016年Elsevier Inc.保留所有权利。

著录项

  • 来源
    《Biochemical Pharmacology》 |2017年第2017期|共14页
  • 作者单位

    King Saud Univ Coll Pharm Dept Pharmacol &

    Toxicol POB 2455 Riyadh 11451 Saudi Arabia;

    King Saud Univ Coll Pharm Dept Pharmacol &

    Toxicol POB 2455 Riyadh 11451 Saudi Arabia;

    King Saud Univ Coll Pharm Dept Pharmacol &

    Toxicol POB 2455 Riyadh 11451 Saudi Arabia;

    King Saud Univ Coll Pharm Dept Pharmacol &

    Toxicol POB 2455 Riyadh 11451 Saudi Arabia;

    King Saud Univ Coll Engn Ind Engn Riyadh Saudi Arabia;

    King Saud Univ Coll Pharm Dept Pharmacol &

    Toxicol POB 2455 Riyadh 11451 Saudi Arabia;

    King Saud Univ Coll Pharm Dept Pharmacol &

    Toxicol POB 2455 Riyadh 11451 Saudi Arabia;

    King Saud Univ Coll Pharm Dept Pharmacol &

    Toxicol POB 2455 Riyadh 11451 Saudi Arabia;

    King Saud Univ Coll Pharm Dept Pharmacol &

    Toxicol POB 2455 Riyadh 11451 Saudi Arabia;

    King Saud Univ Coll Pharm Dept Pharmacol &

    Toxicol POB 2455 Riyadh 11451 Saudi Arabia;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药理学;
  • 关键词

    Psoriasis; Asthma; IL-23; STAT3; Th17;

    机译:牛皮癣;哮喘;IL-23;Stat3;Th17;

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