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灰鼠中耳上皮粘蛋白基因对炎性细胞因子的反应性表达

Chinchilla middle ear epithelial mucin gene expression in response to inflammatory cytokines.

作者信息

Kerschner Joseph E, Meyer Tanya K, Burrows Amy

机构信息

Division of Pediatric Otolaryngology, Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, 9000 W. Wisconsin Avenue, Milwaukee, WI 53226, USA.

出版信息

Arch Otolaryngol Head Neck Surg. 2004 Oct;130(10):1163-7. doi: 10.1001/archotol.130.10.1163.

Abstract

OBJECTIVES

To review the importance of mucin on a molecular level in the understanding of the pathophysiology of otitis media and to present new data demonstrating differential up-regulation of specific mucin genes during inflammation of middle ear epithelium.

DESIGN

Primary chinchilla middle ear epithelial cultures (CMEECs) were established and exposed to tumor necrosis factor alpha and interleukin 1beta. Expression of chinchilla mucin genes 1, 2, 4, and 5AC was analyzed by means of reverse transcriptase-polymerase chain reaction after this exposure and compared with that of controls. Mucin secretion was also characterized by means of exclusion chromatography and liquid scintillation.

RESULTS

The CMEECs exposed to interleukin 1beta and tumor necrosis factor alpha demonstrated significant up-regulation of mucin gene 2 (P = .005 and P = .007, respectively) and trends suggestive of up-regulation of mucin gene 5AC compared with the controls. These CMEECs also demonstrated significant increases in secretion of mucin compared with controls. Mucin genes 1 and 4 did not demonstrate up-regulation.

CONCLUSIONS

In CMEECs, the inflammatory mediators tumor necrosis factor alpha and interleukin 1beta cause a differential up-regulation and expression of mucin genes. Elucidating the effect of specific cytokines on the regulation of mucin secretion in the middle ear is vital to understanding the pathophysiology of otitis media. A greater understanding of these mechanisms and variations between individuals and pathogens has the potential to significantly alter the approach and management of otitis media in children and lead to novel therapeutic interventions.

摘要

目的

在分子水平上综述黏蛋白在理解中耳炎病理生理学中的重要性,并展示新数据,这些数据表明中耳上皮炎症期间特定黏蛋白基因的差异上调。

设计

建立原代龙猫中耳上皮细胞培养物(CMEECs),并将其暴露于肿瘤坏死因子α和白细胞介素1β。暴露后,通过逆转录聚合酶链反应分析龙猫黏蛋白基因1、2、4和5AC的表达,并与对照组进行比较。还通过排阻色谱法和液体闪烁法对黏蛋白分泌进行了表征。

结果

与对照组相比,暴露于白细胞介素1β和肿瘤坏死因子α的CMEECs显示黏蛋白基因2显著上调(分别为P = 0.005和P = 0.007),并且有黏蛋白基因5AC上调的趋势。与对照组相比,这些CMEECs的黏蛋白分泌也显著增加。黏蛋白基因1和4未显示上调。

结论

在CMEECs中,炎症介质肿瘤坏死因子α和白细胞介素1β导致黏蛋白基因的差异上调和表达。阐明特定细胞因子对中耳黏蛋白分泌调节的作用对于理解中耳炎的病理生理学至关重要。对这些机制以及个体和病原体之间差异的更深入了解有可能显著改变儿童中耳炎的治疗方法和管理方式,并带来新的治疗干预措施。

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