Microarray analysis of distinct gene transcription profiles in non-eosinophilic chronic sinusitis with nasal polyps.

Spencer C Payne, Joseph K Han, Phillip Huyett, Julie Negri, Elizabeth Z Kropf, Larry Borish, John W Steinke
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引用次数: 38

Abstract

Background: Recent literature has indicated the feasibility of microarray analysis in the characterization of chronic sinusitis. We hypothesized that previously unexplored inflammatory mechanisms would be involved in the pathophysiology of noneosinophilic chronic rhinosinusitis with nasal polyps (NE-CRSwNP) and that this technology could be used to identify the gene expression of these novel and previously known mediators.

Methods: Patients with CRSwNP failing medical therapy were prospectively enrolled and NP tissue was removed at time of surgery. NE-CRSwNP was diagnosed based on clinical parameters including absence of allergic disease and confirmed with histopathology showing lack of eosinophilic infiltration. Messenger RNA (mRNA) transcripts extracted from study and control patients were then subjected to microarray analysis using Affymatrix based chips. Validation of findings was then confirmed via quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results: Microarray analysis revealed activation of pathways involved in antigen presentation, cellular movement, hematopoiesis, carcinogenesis, apoptosis, and cell signaling. Previously unexplored genes of interest were identified and their differential regulation was validated via qRT-PCR. Our data showed up-regulation of innate inflammation genes (IL-6, IL-8, and monocyte chemoattractant protein 1), hypoxia-induced inflammation 1alpha, and fibrosis (tenascin) and lack of up-regulation of genes associated with allergic, eosinophilic inflammation (IL-4 and IL-13). Additionally, the genes for CXCL1 and autocrine motility factor receptor were novelly identified to be up-regulated.

Conclusion: This study explores the utility of gene microarray technology in identifying unexplored targets of immune dysregulation in NE-CRSwNP. Furthermore, the data characterize the immunologic profile of NE-CRSwNP as it differs from other forms of CRSwNP, in particular, those known to be associated with eosinophilic inflammation.

非嗜酸性慢性鼻窦炎伴鼻息肉不同基因转录谱的微阵列分析。
背景:最近的文献表明微阵列分析在慢性鼻窦炎表征中的可行性。我们假设以前未探索的炎症机制将参与非嗜酸性慢性鼻窦炎伴鼻息肉(NE-CRSwNP)的病理生理,并且该技术可用于鉴定这些新的和先前已知的介质的基因表达。方法:前瞻性纳入药物治疗失败的CRSwNP患者,手术时切除NP组织。NE-CRSwNP是根据临床参数诊断的,包括没有过敏性疾病,并通过组织病理学证实缺乏嗜酸性粒细胞浸润。然后使用基于Affymatrix的芯片对从研究和对照患者中提取的信使RNA (mRNA)转录本进行微阵列分析。然后通过定量逆转录聚合酶链反应(qRT-PCR)确认结果的有效性。结果:微阵列分析揭示了抗原呈递、细胞运动、造血、癌变、凋亡和细胞信号通路的激活。先前未探索的感兴趣的基因被鉴定出来,并通过qRT-PCR验证了它们的差异调控。我们的数据显示先天炎症基因(IL-6、IL-8和单核细胞趋化蛋白1)、缺氧诱导的炎症1 α和纤维化(tenascin)上调,而与过敏性、嗜酸性炎症相关的基因(IL-4和IL-13)缺乏上调。此外,CXCL1和自分泌运动因子受体的基因也被新发现上调。结论:本研究探索了基因微阵列技术在鉴定NE-CRSwNP中未被发现的免疫失调靶点中的应用。此外,这些数据表征了NE-CRSwNP的免疫学特征,因为它不同于其他形式的CRSwNP,特别是那些已知与嗜酸性粒细胞炎症相关的CRSwNP。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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