Hemokinin-1 stimulates C-C motif chemokine ligand 24 production in macrophages to enhance eosinophilic inflammation in nasal polyps
Hemokinin-1 stimulates C-C motif chemokine ligand 24 production in macrophages to enhance eosinophilic inflammation in nasal polyps
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Hemokinin-1 刺激巨噬细胞中 C-C 基序趋化因子配体 24 的产生，从而增强鼻息肉中的嗜酸性粒细胞炎症
DOI：
10.1002/alr.22430
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发表时间：
2019
影响因子：
6.4
通讯作者：
Liu Zheng
中科院分区：
文献类型：
--
作者：
Deng Yi-Ke;Ma Jin;Wang Zhi-Chao;Long Xiao-Bo;Chen Cai-Ling;Feng Qi-Miao;Zhang Xin-Hao;Zeng Ming;Wang Heng;Lu Xiang;Liu Zheng
背景慢性鼻窦炎伴鼻息肉（CRSwNP）黏膜嗜酸性粒细胞增多的机制尚不清楚。神经系统和神经肽在免疫应答的调节中起着重要作用。在此，我们探讨血激肽-1（HK-1），一种新发现的速激肽，沿着其受体神经激肽1受体（NK 1 R）在CRSwNP中的表达和功能。（53例嗜酸性CRSwNP，32例非嗜酸性CRSwNP，通过定量逆转录聚合酶链反应（RT-PCR）和免疫荧光染色研究了33例对照组）。用HK-1刺激人单核细胞白血病细胞系THP-1和嗜酸性息肉组织。随后收集细胞、组织和培养上清，通过定量RT-PCR和酶联免疫法检测各种炎性细胞因子和趋化因子的产生。结果与对照组织相比，嗜酸性和非嗜酸性鼻息肉中HK-1和NK 1 R mRNA和蛋白表达上调，嗜酸性息肉的上调程度高于非嗜酸性息肉。嗜酸性粒细胞构成HK-1的主要来源，而巨噬细胞是嗜酸性息肉中表现出NK 1 R的主要细胞类型。HK-1诱导从THP-1细胞分化的巨噬细胞产生CCL 24;这被NK 1 R拮抗剂消除。HK-1还诱导离体培养的嗜酸性鼻息肉产生CCL 24。CCL 24由嗜酸性而非非嗜酸性息肉中的巨噬细胞表达。HK-1的表达水平与嗜酸性鼻息肉中的CCL 24表达和组织嗜酸性粒细胞相关。结论嗜酸性粒细胞来源的HK-1诱导巨噬细胞产生CCL 24，因此加剧了CRSwNP中的嗜酸性炎症。
BackgroundThe mechanisms underlying mucosal eosinophilia in chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly clarified. The nervous system and neuropeptides play an important role in the regulation of immune response. Herein we explore the expression and function of hemokinin‐1 (HK‐1), a newly identified tachykinin, along with its receptor neurokinin 1 receptor (NK1R) in CRSwNP.MethodsHK‐1, NK1R, and C‐C motif chemokine ligand 24 (CCL24) expression in nasal tissues (53 eosinophilic CRSwNP, 32 non‐eosinophilic CRSwNP, and 33 controls) was investigated by quantitative reverse transcript polymerase chain reaction (RT‐PCR) and immunofluorescence staining. THP‐1, a human monocytic leukemia cell line, and eosinophilic polyp tissues were stimulated with HK‐1. Cells, tissues, and culture supernatants were subsequently collected for detection of the production of various inflammatory cytokines and chemokines by quantitative RT‐PCR and enzyme‐linked immunoassay.ResultsHK‐1 and NK1R mRNA and protein expression were upregulated in eosinophilic and non‐eosinophilic nasal polyps compared with control tissues, with eosinophilic polyps demonstrating a higher upregulation compared with that of non‐eosinophilic polyps. Eosinophils constituted the major source of HK‐1, whereas macrophages were the predominant cell type exhibiting NK1R in eosinophilic polyps. HK‐1 induced CCL24 production from macrophages differentiated from THP‐1 cells; this was abolished by an NK1R antagonist. HK‐1 also induced CCL24 production from ex vivo‒cultured eosinophilic nasal polyps. CCL24 was expressed by macrophages in eosinophilic but not non‐eosinophilic polyps. The expression level of HK‐1 correlated with CCL24 expression and tissue eosinophilia in eosinophilic nasal polyps.ConclusionEosinophil‐derived HK‐1 induces CCL24 production from macrophages and therefore exaggerates eosinophilic inflammation in CRSwNP.