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SGK1 enhances Th9 cell differentiation and airway inflammation through NF-kappa B signaling pathway in asthma

机译:通过在哮喘中通过NF-Kappa B信号通路增强Th9细胞分化和气道炎症

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摘要

This study aimed to explore the effect of Sgk1 on Th9 differentiation and the underlying mechanism in asthma. The asthmatic mouse model induced by ovalbumin (OVA) and CD4(+)T cells which were cultured with TGF-beta, IL-2, IL-4, and anti-IFN-gamma were applied in vivo and in vitro, respectively. Flow cytometry, quantitative real-time PCR (qRT-PCR), and ELISA were performed to detect T-helper 9 (Th9) cells, IL-9 expression, and IL-9 release. Western blot was performed to examine phosphorylated(p)-IKK alpha, p-I kappa B alpha, p-p65, and IRF4 levels. Hematoxylin/eosin (H&E) staining was adopted to assess pathological changes of lung tissues. Inhibition of Sgk1 dramatically reversed elevated Th9 cells and IL-9 expression in the lung tissues of asthmatic mice. In vitro, Sgk1 promoted Th9 differentiation and elevated p-IKK alpha, p-I kappa B alpha, p-p65, and IRF4 levels, but inhibition of IKK alpha/I kappa B alpha/p65 pathway and IRF4 both reversed enhanced Th9 differentiation by Sgk1. Sgk1 -> IKK alpha/I kappa B alpha/NF-kappa Bp65 -> IRF4 -> Th9 axis may be implicated in asthma development.
机译:本研究旨在探讨Sgk1对Th9分化的影响及其在哮喘中的潜在机制。将卵蛋白(OVA)和CD4(+)T细胞与TGF-β、IL-2、IL-4和抗IFN-γ一起培养,分别在体内和体外建立哮喘小鼠模型。流式细胞术、实时定量PCR(qRT PCR)和ELISA检测辅助性T细胞9(Th9)细胞、IL-9表达和IL-9释放。Western blot检测磷酸化(p)-IKKα、p-IκBα、p-p65和IRF4水平。苏木精/伊红(H&E)染色用于评估肺组织的病理变化。抑制Sgk1可显著逆转哮喘小鼠肺组织中升高的Th9细胞和IL-9表达。在体外,Sgk1促进Th9分化,提高p-IKKα、p-IκBα、p-p65和IRF4水平,但抑制IKKα/IκBα/p65途径和IRF4均逆转了Sgk1增强的Th9分化。Sgk1->IKKα/IκBα/NFκBp65->IRF4->Th9轴可能与哮喘的发展有关。

著录项

  • 来源
    《Cell and Tissue Research》 |2020年第3期|共12页
  • 作者单位

    Harbin Med Univ Dept Pediat Affiliated Hosp 2 246 Xuefu Rd Harbin 150001 Heilongjiang Peoples;

    Harbin Med Univ Dept Pediat Affiliated Hosp 2 246 Xuefu Rd Harbin 150001 Heilongjiang Peoples;

    Qingdao Women &

    Childrens Hosp Dept Pneumol Qingdao 266000 Shandong Peoples R China;

    Harbin Med Univ Dept Pediat Affiliated Hosp 2 246 Xuefu Rd Harbin 150001 Heilongjiang Peoples;

    Harbin Med Univ Dept Pediat Affiliated Hosp 2 246 Xuefu Rd Harbin 150001 Heilongjiang Peoples;

    Harbin Med Univ Dept Pediat Affiliated Hosp 2 246 Xuefu Rd Harbin 150001 Heilongjiang Peoples;

    Harbin Med Univ Dept Pediat Affiliated Hosp 2 246 Xuefu Rd Harbin 150001 Heilongjiang Peoples;

    Harbin Med Univ Dept Pediat Affiliated Hosp 2 246 Xuefu Rd Harbin 150001 Heilongjiang Peoples;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    Sgk1; Th9 cell differentiation; IKK alpha; I kappa B alpha; p65; IRF4; Asthma;

    机译:sgk1;th9细胞分化;ikk alpha;i kappa b alpha;p65;IRF4;哮喘;

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