Enhanced expression of interleukin-8 and activation of nuclear factor kappa-B in endoscopy-negative gastroesophageal reflux disease
Enhanced expression of interleukin-8 and activation of nuclear factor kappa-B in endoscopy-negative gastroesophageal reflux disease
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DOI：
10.1111/j.1572-0241.2004.04110.x
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发表时间：
2004-04-01
影响因子：
9.8
通讯作者：
Kohno, S
中科院分区：
文献类型：
--
作者：
Isomoto, H;Saenko, VA;Kohno, S
目的：白细胞介素-8（IL-8）通过其受体介导中性粒细胞的转运。近年来的研究表明IL-8可能参与了糜烂性反流性食管炎（RE）的发生和发展，但其在内镜阴性胃食管反流病（GERD）中的意义尚不清楚。本研究的目的是确定IL-8信使核糖核酸（mRNA）的表达水平在内镜阴性GERD，沿着与核因子κ B（NF-κ B）的活化，上调IL-8 expression.METHODS：我们研究了31例内镜阴性GERD，15例糜烂性RE，15例无症状对照。从食管胃食管交界处上方3 cm处采集成对活检样本;一份活检样本快速冷冻，通过实时定量聚合酶链反应测量IL-8 mRNA水平，另一份活检样本福尔马林固定，进行组织病理学评价。在9例内镜阴性GERD患者中，在兰索拉唑治疗前和治疗后8周测定IL-8 mRNA表达水平。结果：内镜阴性GERD患者食管黏膜中IL-8 mRNA的相对表达水平明显高于对照组，且与对照组比较差异有统计学意义（P < 0. 05）。基底层增生和上皮内中性粒细胞的存在，GERD的组织病理学标志，与IL-8 mRNA的水平较高。兰索拉唑治疗显著降低了IL-8 mRNA表达水平。GERD患者的食管上皮显示强烈的IL-8免疫反应性，并表达CXCR-1抗原。我们发现NF-κ B激活食管黏膜GERD患者和NF-κ B亚单位主要定位于细胞核中的IL-8-expressing cells.CONCLUSIONS：我们的研究结果表明，增强粘膜表达IL-8在早期GERD，即使没有粘膜破损。NF-kappaB活化可能与GERD的发病机制有关。
OBJECTIVE: Interleukin-8 (IL-8) mediates neutrophil trafficking via its receptors. Recent studies have shown that IL-8 is likely involved in the development and progression of erosive reflux esophagitis (RE), yet little is known about its implication in endoscopy-negative gastroesophageal reflux disease (GERD). The purpose of this study was to determine IL-8 messenger ribonucleic acid (mRNA) expression levels in endoscopy-negative GERD, along with assessment of nuclear factor kappaB (NF-kappaB) activation, which upregulates IL-8 expression.METHODS: We studied 31 patients with endoscopy-negative GERD, 15 patients with erosive RE, and 15 asymptomatic controls. Paired biopsy samples were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap-frozen for measurement of IL-8 mRNA levels by real-time quantitative polymerase chain reaction, and another was formalin-fixed for histopathological evaluation. In nine endoscopy-negative GERD patients, the IL-8 mRNA expression levels were measured before and 8 wk after treatment with lansoprazole. We also sampled additional specimens for NF-kappaB-DNA binding assay and immunohistochemical analyses of NF-kappaB p65 and p50 subunits, IL-8 and specific IL-8 receptor, CXCR-1.RESULTS: The relative IL-8 mRNA expression levels were significantly higher in esophageal mucosa of patients with endoscopy-negative GERD than those of the controls. The presence of basal zone hyperplasia and intraepithelial neutrophils, histopathological hallmarks of GERD, were associated with higher levels of IL-8 mRNA. Lansoprazole treatment significantly reduced the IL-8 mRNA expression levels. The esophageal epithelium of patients with GERD showed intense immunoreactivity for IL-8, and expressed CXCR-1 antigen. We found NF-kappaB activation in esophageal mucosa in GERD patients and the NF-kappaB subunits were localized predominantly in the nuclei of IL-8-expressing cells.CONCLUSIONS: Our results demonstrate enhanced mucosal expression of IL-8 in incipient GERD even without mucosal breaks. NF-kappaB activation may be implicated in the pathogenesis in GERD.