Tc17/IL-17A Up-Regulated the Expression of MMP-9 via NF-κB Pathway in Nasal Epithelial Cells of Patients With Chronic Rhinosinusitis.
Tc17/IL-17A Up-Regulated the Expression of MMP-9 via NF-κB Pathway in Nasal Epithelial Cells of Patients With Chronic Rhinosinusitis.
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Tc17/IL-17A通过NF-κB通路上调慢性鼻窦炎患者鼻上皮细胞MMP-9的表达
DOI：
10.3389/fimmu.2018.02121
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发表时间：
2018
影响因子：
7.3
通讯作者：
Zhang G
中科院分区：
文献类型：
--
作者：
Chen X;Chang L;Li X;Huang J;Yang L;Lai X;Huang Z;Wang Z;Wu X;Zhao J;Bellanti JA;Zheng SG;Zhang G
慢性鼻窦炎是一种常见的累及鼻腔和鼻窦的上呼吸道慢性炎症性疾病。由于CRS临床表现的复杂性和发病机制的异质性，导致其发病的分子机制尚不清楚，引起了广泛的关注。目前的证据表明，IL-17 A在慢性鼻窦炎伴鼻息肉（CRSwNP）中高表达。然而，其在调节CRSwNP的组织重塑中的发病作用仍然未知。本研究旨在探讨IL-17 A细胞因子在CRSwNP中的细胞来源和功能，并进一步探讨IL-17 A是否影响CRSwNP的重塑因子--金属蛋白酶（MMPs）的表达。结果显示，与慢性鼻窦炎无鼻息肉（CRSsNP）和对照组相比，CRSwNP患者鼻组织中IL-17 A的表达上调。CD 8+细胞毒性T淋巴细胞（Tc）是CRSwNP鼻组织中IL-17 A的主要产生者。CRSwNP鼻组织中产生白细胞介素（IL）-17的CD 8 + T细胞（Tc 17）显著高于CRSsNP和对照。然而，在这三组的外周血淋巴细胞中的IL-17 A之间没有观察到差异。此外，在相同的患者中，与鼻组织相比，外周血淋巴细胞中的IL-17 A表达可忽略不计。与对照组相比，CRSwNP患者MMP-7和MMP-9的基因和蛋白表达增加。在CRSwNP中，IL-17 A受体（IL-17 AR）与MMP-9共定位，并且它们主要在上皮细胞中表达。MMP-9表达在原代人鼻上皮细胞（PHNECs）和鼻上皮细胞系（RPMI 2650）中通过IL-17 A处理上调，并且通过抗IL-17 AR处理降低。IL-17 A通过激活NF-κB信号通路促进MMP-9的表达。因此，我们的研究结果揭示了IL-17 A和Tc细胞在CRSwNP的发病机制和组织重塑中的关键作用。
Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease of the upper airways involving nasal cavity and sinus. Deriving both from its clinical complexity with protean clinical manifestations as well its pathogenetic heterogeneity, the molecular mechanisms contributing to the pathogenesis of CRS remain unclear, and attract a wide interest in the field. Current evidences indicate that IL-17A is highly expressed in chronic rhinosinusitis with nasal polyps (CRSwNP). However, its pathogenetic role in regulation of tissue remodeling of CRSwNP remains unknown. The present study aimed to investigate the cellular origins and functions of IL-17A cytokine in CRSwNP, and further determined whether IL-17A could affect the expression of metalloproteinases (MMPs), the remodeling factors of CRSwNP. The results showed that the expression of IL-17A was upregulated in nasal tissues of patients with CRSwNP compared to those with chronic rhinosinusitis without nasal polyps (CRSsNP) and controls. CD8+ cytotoxic T lymphocytes (Tc) were major IL-17A producers in nasal tissues of CRSwNP. Interleukin (IL)-17-producing CD8+ T cells (Tc17) was significantly higher in nasal tissues of CRSwNP than CRSsNP and controls. Nonetheless, no difference was observed among the IL-17A in peripheral blood lymphocytes of these three groups. Moreover, in the same patients, IL-17A expression was negligible in lymphocytes of peripheral blood when compared with nasal tissues. Increased gene and protein expression of MMP-7 and MMP-9 in patients with CRSwNP compared with controls were observed. In CRSwNP samples, IL-17A receptor (IL-17AR) co-localized with MMP-9 and they were mainly expressed in the epithelial cells. MMP-9 expression was up-regulated both in Primary human nasal epithelial cells (PHNECs) and a nasal epithelial cell line (RPMI 2650) by IL-17A treatment, and diminished by anti-IL-17AR treatment. Furthermore, IL-17A promoted the expression of MMP-9 by activating the NF-κB signal pathway. Thus, our results have revealed a crucial role of IL-17A and Tc cells on pathogenesis and tissue remodeling of CRSwNP.
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DOI：
10.1186/s13223-016-0123-3
发表时间：
2016
期刊：
Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology
影响因子：
--
作者：
König K;Klemens C;Haack M;Nicoló MS;Becker S;Kramer MF;Gröger M
通讯作者：
Gröger M
DOI：
10.4049/jimmunol.0801814
发表时间：
2009-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hamada H;Garcia-Hernandez Mde L;Reome JB;Misra SK;Strutt TM;McKinstry KK;Cooper AM;Swain SL;Dutton RW
通讯作者：
Dutton RW
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：
4.3
作者：
Kang, Hyereen;Jang, Sung-Wuk;Pak, Jhang Ho;Shim, Sungbo
通讯作者：
Shim, Sungbo
影响因子：
3.4
作者：
Hao, J;Pang, YT;Wang, DY
通讯作者：
Wang, DY