IL-17 Enhances Chemotaxis of Primary Human B Cells during Asthma.

IL-17 Enhances Chemotaxis of Primary Human B Cells during Asthma.
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IL-17在哮喘期间增强了原代人B细胞的趋化性。

DOI:
10.1371/journal.pone.0114604
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Al-Muhsen S
Al-Muhsen S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Halwani R;Al-Kufaidy R;Vazquez-Tello A;Pureza MA;BaHammam AS;Al-Jahdali H;Alnassar SA;Hamid Q;Al-Muhsen S

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IL-17是促炎介质,被认为在哮喘、COPD以及其他炎性疾病期间在调节组织炎症中起关键作用。IL-17的表达水平已显示在哮喘患者的肺支气管组织中上调。一些报告提供了进一步的证据,这种细胞因子可以在增强哮喘和COPD期间支气管肺组织的炎性细胞和结构细胞的迁移中发挥关键作用。已经报道了在炎性疾病如肠病、哮喘和COPD期间B细胞浸润至炎症部位。因此,在本研究中,我们假设IL-17可能在哮喘期间对原代B细胞发挥趋化作用。我们观察到,与健康受试者相比,哮喘患者的B细胞表达的IL-17 RA和IL-17 RC水平显着更高。使用体外迁移测定,显示B细胞向IL-17 A和IL-17 F迁移。有趣的是,使用抗IL-17 R抗体或MAP激酶抑制剂阻断IL-17 A和IL-17 F信号传导阻止了B细胞向IL-17的体外迁移。这些观察结果表明IL-17细胞因子对原代外周血B细胞具有直接趋化作用,其中对哮喘B细胞的作用更高。这些发现揭示了IL-17在哮喘或COPD期间增强B细胞向肺组织迁移中的关键作用。
IL-17 is a pro-inflammatory mediator that is believed to play a critical role in regulating tissue inflammation during asthma, COPD, as well as other inflammatory disorders. The level of expression of IL-17 has been shown to be upregulated in lung bronchial tissue of asthmatic patients. Several reports have provided further evidence that this cytokine could play a key role in enhancing the migration of inflammatory as well as structural cells of the bronchial lung tissue during asthma and COPD. B cell infiltration to sites of inflammation during inflammatory disorders such as bowel disease, asthma and COPD has been reported. Accordingly, in this study we hypothesized that IL-17 may exert a chemotactic effect on primary B cells during asthma. We observed that B cells from asthmatic patients expressed significantly higher levels of IL-17RA and IL-17RC, compared to those of healthy subjects. Using an in-vitro migration assay, B cells were shown to migrate towards both IL-17A and IL-17F. Interestingly, blocking IL-17A and IL-17F signaling using either anti-IL-17R antibodies or MAP kinase inhibitors prevented in vitro migration of B cell towards IL-17. These observations indicate a direct chemotactic effect of IL-17 cytokines on primary peripheral blood B cells with higher effect being on asthmatic B cells. These findings revealed a key role for IL-17 in enhancing the migration of B cells to the lung tissue during asthma or COPD.
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