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人喉鳞状癌细胞中NKG2D配体的表达及NKG2D介导的细胞毒性

NKG2D ligands expression and NKG2D-mediated cytotoxicity in human laryngeal squamous carcinoma cells.

作者信息

Chen X M, Xu X Q, Sun K, Hallett W H D, Zhao J D, Zhang D L

机构信息

Department of Otolaryngology, the Second Affiliated Hospital of Shandong University, Jinan, China.

出版信息

Scand J Immunol. 2008 May;67(5):441-7. doi: 10.1111/j.1365-3083.2008.02086.x. Epub 2008 Feb 27.

Abstract

The NKG2D is an activating immunoreceptor expressed by NK cells and CD8(+) T cells. Engagement of NKG2D by its ligands is critical for both innate and adoptive immunity. While the overexpression of NKG2D ligands on certain tumour cells has previously been demonstrated, little is known about NKG2D ligand expression on human laryngeal tumour cells. In this study, we first verified that the interaction between NKG2D and its ligands was critical for NK cell-based immune response to human laryngeal squamous carcinoma cells Hep-2. This NKG2D-mediated effect was observed by transfecting the recombinant eukaryotic expression vector pEGFP-N1/NKG2D as well as the NKG2D blockade. The mRNA and protein expression of NKG2D ligands, MHC class I-related chain molecules A (MICA) and UL16-binding proteins (ULBPs), in human laryngeal carcinoma cell line Hep-2 and fresh tumour tissues were evaluated. Compared with non-tumour tissues of vocal cords polyps, MICA and ULBP-3 were strongly overexpressed on both the human laryngeal carcinoma cell line Hep-2 and fresh human laryngeal carcinoma tissues. The mechanism and impact of NKG2D ligands overexpression on NK cell-mediated anti-laryngeal cancer immune response would require further investigation.

摘要

NKG2D是一种由自然杀伤细胞(NK细胞)和CD8(+) T细胞表达的激活型免疫受体。NKG2D与其配体的结合对于先天免疫和过继性免疫均至关重要。虽然此前已证实在某些肿瘤细胞上过表达NKG2D配体,但对于人喉肿瘤细胞上NKG2D配体的表达情况却知之甚少。在本研究中,我们首先证实NKG2D与其配体之间的相互作用对于基于NK细胞的针对人喉鳞状癌细胞Hep-2的免疫反应至关重要。通过转染重组真核表达载体pEGFP-N1/NKG2D以及进行NKG2D阻断,观察到了这种由NKG2D介导的效应。评估了人喉癌细胞系Hep-2和新鲜肿瘤组织中NKG2D配体、主要组织相容性复合体I类相关链分子A(MICA)和UL16结合蛋白(ULBP)的mRNA和蛋白表达。与声带息肉的非肿瘤组织相比,MICA和ULBP-3在人喉癌细胞系Hep-2和新鲜人喉癌组织中均强烈过表达。NKG2D配体过表达对NK细胞介导的抗喉癌免疫反应的机制和影响还有待进一步研究。

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