Enhanced Interferon-β Response Contributes to Eosinophilic Chronic Rhinosinusitis.
Enhanced Interferon-β Response Contributes to Eosinophilic Chronic Rhinosinusitis.
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DOI：
10.3389/fimmu.2018.02330
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发表时间：
2018
影响因子：
7.3
通讯作者：
Kim JH
中科院分区：
文献类型：
--
作者：
Jang YJ;Lim JY;Kim S;Lee Y;Kweon MN;Kim JH
I型干扰素（IFN-1，包括IFN-α和IFN-β）反应除了抗病毒功能外，还与嗜酸性粒细胞炎症有关。本研究旨在探讨干扰素-I在嗜酸性粒细胞性慢性鼻窦炎（ECRS）发病机制中的作用。采用真实的时间PCR、ELISA和免疫组织化学方法检测正常对照组和鼻息肉患者（NP）鼻窦组织中IFN-α、IFN-β、细胞因子的表达和IFN-β的细胞定位。在野生型（WT）和IFNAR 1敲除（Ifnar 1 −/−）小鼠中，通过曲霉蛋白酶和卵清蛋白鼻内激发诱导ECRS。用外源性IFN-β刺激从NP组织培养的基质细胞，并测量它们的CCL 11产生和IRF 3、IRF 7、STAT 1、STAT 2和IRF 9基因和/或蛋白表达。与对照组相比，ECRS患者NP组织中IFN-β、IL-5、IL-13和CCL 11的表达更高。IFN-β与NP中的CD 11 c+细胞高度共定位。IFN-β水平与IL-5、IL-13和CCL 11水平以及NP组织中嗜酸性粒细胞数量和CT评分呈正相关。Ifnar 1 −/−小鼠中ECRS的组织学严重程度、鼻灌洗液中IL-4、IL-5、IL-13和CCL 11的水平以及总血清IgE水平均低于WT小鼠。外源性IFN-β可显著增加NP基质细胞中CCL 11的产生、STAT 1和STAT 2 mRNA以及STAT 1、磷酸化STAT 1和磷酸化STAT 2蛋白的表达。我们的数据表明，IFN-β反应在ECRS中上调，并可能在ECRS的发展中发挥作用。IFN-β可能通过促进CCL 11的产生而促进ECRS。因此，鼻粘膜中IFN-β反应的增加可能是ECRS发病机制的基础。
Type I interferon (IFN-I, including IFN-α and IFN-β) response has been implicated in eosinophilic inflammation, in addition to antiviral function. This study aimed to investigate the role of IFN-I in the pathogenesis of eosinophilic chronic rhinosinusitis (ECRS). IFN-α, IFN-β, cytokine expression, and IFN-β cellular localization in the sinonasal tissue from control subjects and ECRS patients with nasal polyps (NP) were determined using real time-PCR, ELISA, and immunohistochemistry. ECRS was induced in wild-type (WT) and IFNAR1 knockout (Ifnar1−/−) mice by intranasal challenge with Aspergillus protease and ovalbumin. Stromal cells cultured from NP tissue were stimulated by exogenous IFN-β, and their CCL11 production and IRF3, IRF7, STAT1, STAT2, and IRF9 gene and/or protein expression were measured. IFN-β, IL-5, IL-13, and CCL11 expression was higher in the NP tissue from ECRS patients, compared to the control group. IFN-β was highly colocalized with the CD11c+ cells in NP. IFN-β levels positively correlated with IL-5, IL-13, and CCL11 levels as well as the number of eosinophils in the NP tissue and CT score. The histological severity of ECRS, levels of IL-4, IL-5, IL-13, and CCL11 in the nasal lavage fluid, and total serum IgE levels were less in Ifnar1−/− mice than in WT mice. CCL11 production, and STAT1 and STAT2 mRNA and STAT1, phospho-STAT1, and phospho-STAT2 protein expression were significantly increased by exogenous IFN-β in NP stromal cells. Our data suggest that IFN-β response was upregulated in ECRS and may play role in ECRS development. IFN-β may contribute to ECRS by enhancing CCL11 production. Thus, increased IFN-β response in the sinonasal mucosa may underlie ECRS pathogenesis.
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影响因子：
2.8
作者：
Matsumoto, K;Terakawa, M;Saito, H
通讯作者：
Saito, H
影响因子：
4.6
作者：
Kim JH;Choi GE;Lee BJ;Kwon SW;Lee SH;Kim HS;Jang YJ
通讯作者：
Jang YJ
影响因子：
7.2
作者：
Fokkens, Wytske J.;Lund, Valerie J.;Wormald, Peter John
通讯作者：
Wormald, Peter John
影响因子：
3.6
作者：
Martin-Saavedra, Francisco M.;Gonzalez-Garcia, Coral;Ballester, Sara
通讯作者：
Ballester, Sara
DOI：
10.4161/jkst.23931
发表时间：
2013-07-01
期刊：
JAK-STAT
影响因子：
--
作者：
Au-Yeung N;Mandhana R;Horvath CM
通讯作者：
Horvath CM