IL-27 attenuates airway inflammation in a mouse asthma model via the STAT1 and GADD45γ/p38 MAPK pathways.
IL-27 attenuates airway inflammation in a mouse asthma model via the STAT1 and GADD45γ/p38 MAPK pathways.
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IL-27 通过 STAT1 和 GADD45 gamma/p38 MAPK 通路减轻小鼠哮喘模型中的气道炎症
DOI：
10.1186/s12967-016-1039-x
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发表时间：
2016-09-29
影响因子：
7.4
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Su X;Pan J;Bai F;Yuan H;Dong N;Li D;Wang X;Chen Z
哮喘易于发生Th 2介导的慢性气道炎症。白细胞介素-27（IL-27）是IL-12家族的成员，其促进Th 1细胞的分化并抑制Th 2细胞。本研究采用人/鼠CD 4 + T细胞观察IL-27是否能抑制IL-4的产生，并通过小鼠哮喘模型观察IL-27是否能减轻过敏性气道炎症。我们分离并培养了健康人和小鼠的CD 4 + T细胞，以测试IL-27是否可以在不同条件下抑制IL-4的产生。在体内研究中，使用两种类型的鼻内（i. n.）给药：在鼠哮喘模型中低剂量多次预防或高剂量有限次治疗。采用qPCR和Western blotting方法检测肺组织中信号转导和转录激活因子1（STAT 1）和生长停滞与DNA损伤45-γ（GADD 45 γ）/p38丝裂原活化蛋白激酶（p38 MAPK）的表达水平。IL-27在体外虽能抑制幼稚CD 4 + T细胞向Th 2细胞分化，但不能使已定型的Th 2细胞再分化。在体内，IL-27的预防性给药减弱了过敏性炎症和气道高反应性，而治疗组没有显著效果。哮喘组STAT 1磷酸化受损，GADD 45 γ和p38 MAPK无明显变化。IL-27干预可逆转STAT 1的损伤，增强GADD 45 γ和p38 MAPK的表达，而治疗组无明显影响。IL-27通过STAT 1和GADD 45 γ/p38 MAPK途径改善哮喘小鼠模型的病理变化，而IL-27治疗性给药没有显著影响，这可能是由于哮喘气道中存在抵抗IL-27抑制的已分化的Th 2细胞。本文的在线版本（doi：10.1186/s12967-016-1039-x）包含补充材料，可供授权用户使用。
Asthma is prone to Th2-mediated chronic airway inflammation. Interleukin-27 (IL-27) is a member of the IL-12 family that promotes the differentiation of Th1 cells and inhibits Th2 cells. We use human/mouse CD4+ T cells to see whether IL-27 could inhibit IL-4 production in vitro and then observe whether IL-27 administration could alleviate allergic airway inflammation in vivo by mice asthma model. We isolated and cultured CD4+ T cells from healthy humans and mice to test whether IL-27 could inhibit IL-4 production under different conditions. In vivo study, the effect of IL-27 was examined using two types of intra-nasal (i.n.) administration: low-dose-multiple-times prevention or high-dose-limited-times treatment in murine asthma models. The expression levels of signal transducer and activator of transcription-1 (STAT1) and growth arrest and DNA damage 45-γ (GADD45γ)/p38 mitogen activated protein kinase (p38 MAPK) in lung tissues were measured using qPCR and Western blotting. In vitro, although IL-27 could inhibit naïve CD4+ T cell differentiate into Th2 cells, but it could not redifferentiate already committed Th2 cells. In vivo, preventative administration of IL-27 attenuated allergic inflammation and airway hyperreactivity, whereas treatment group had no significant effect. In the asthma group, the phosphorylation of STAT1 was impaired, while GADD45γ and p38 MAPK exhibited no obvious changes. Preventative administration of IL-27 could either reverse the impairment of STAT1 or strengthen the expression of GADD45γ and p38 MAPK, whereas treatment group had no significant effect. Preventative administration of IL-27 improved the pathological changes in mouse asthma models via both the STAT1 and GADD45γ/p38 MAPK pathways while therapeutic administration of IL-27 had no significant effect, which may be due to the presence of already differentiated Th2 cells in asthmatic airways that resist IL-27 inhibition. The online version of this article (doi:10.1186/s12967-016-1039-x) contains supplementary material, which is available to authorized users.
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影响因子：
30.8
作者：
Dupuis, S;Jouanguy, E;Casanova, JL
通讯作者：
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影响因子：
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作者：
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