Alternatively activated macrophages promote airway inflammation through JAK3–STAT5–Fra2 in asthma,Inflammation Research

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Alternatively activated macrophages promote airway inflammation through JAK3–STAT5–Fra2 in asthma
Inflammation Research ( IF 4.8 ) Pub Date : 2022-06-07 , DOI: 10.1007/s00011-022-01585-z
Siyuan Huang ₁ , Jing Wang ₁ , Fen Liu ₂ , Liang Dong ₂

Affiliation

Background

Fos-related antigen-2 (Fra-2) is a transcription factor belonging to the activator protein 1 (AP-1) family, which is associated with many chronic airway diseases such as asthma. Alternatively activated (M2) macrophages are associated with Fra2 in airway diseases such as pulmonary fibrosis. However, there is no specific study that explores the relationship between M2 macrophages and Fra2 in asthma.

Objective

We hypothesized that a potential mechanism of allergic asthma could be that Fra2 is highly expressed in M2 macrophages through JAK3–STAT5 and facilitates the production of downstream T-helper 2 (Th2) cytokines, thus promoting the pathogenesis of asthma.

Methods

Peripheral venous blood and airway tissue samples of patients with asthma and controls were obtained. Moreover, a C57BL/6 mouse model of asthma was established. Fra2 expression was detected using immunohistochemistry and immunofluorescence. Macrophages were obtained by flow sorting, and expression of the JAK3–STAT5–Fra2 signaling pathway was determined using PCR and western blotting. Enzyme-linked immunosorbent assay was used to determine M2 macrophage-associated Th2-type cytokine levels.

Results

Fra2 was highly expressed in patients with asthma and asthmatic mice. The JAK3–STAT5 was a signal pathway related to the high expression of Fra2 in M2 macrophages. Moreover, we found that Fra2 could affect the production of Th2 cytokines downstream of M2 macrophages, including interleukin 4 (IL-4) and IL-13.

Conclusion

M2 macrophages could promote airway inflammation through JAK3–STAT5–Fra2 to induce allergic asthma. Our study offers a new insight to further understand the pathogenesis of asthma and also provides a new direction for targeted treatment.

中文翻译：

或者激活的巨噬细胞通过 JAK3-STAT5-Fra2 在哮喘中促进气道炎症

背景

Fos 相关抗原 2 (Fra-2) 是属于激活蛋白 1 (AP-1) 家族的转录因子，与哮喘等许多慢性气道疾病有关。或者激活的 (M2) 巨噬细胞与肺纤维化等气道疾病中的 Fra2 相关。然而，没有具体的研究探讨哮喘中 M2 巨噬细胞和 Fra2 之间的关系。

客观的

我们假设过敏性哮喘的一个潜在机制可能是 Fra2 通过 JAK3-STAT5 在 M2 巨噬细胞中高表达，并促进下游 T 辅助细胞 2 (Th2) 细胞因子的产生，从而促进哮喘的发病机制。

方法

获得哮喘患者和对照组的外周静脉血和气道组织样本。此外，建立了C57BL/6小鼠哮喘模型。使用免疫组织化学和免疫荧光检测 Fra2 的表达。通过流式分选获得巨噬细胞，并使用 PCR 和蛋白质印迹测定 JAK3-STAT5-Fra2 信号通路的表达。酶联免疫吸附试验用于确定 M2 巨噬细胞相关的 Th2 型细胞因子水平。