Rhinovirus infection induces expression of its own receptor intercellular adhesion molecule 1 (ICAM-1) via increased NF-κB-mediated transcription

作     者：Papi, A Johnston, SL 

作者机构：Univ Southampton Southampton Gen Hosp Southampton SO16 6YD Hants England 

出 版 物：《JOURNAL OF BIOLOGICAL CHEMISTRY》 (生物化学杂志)

年 卷 期：1999年第274卷第14期

页      面：9707-9720页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 

主　　题：哮喘/并发症 哮喘/病毒学 结合部位 支气管/代谢 支气管/病毒学 细胞系 上皮细胞/代谢 上皮细胞/病毒学 胞间黏附分子1/生物合成 NF-κB/代谢 细小RNA病毒科感染/并发症 细小RNA病毒科感染/代谢 细小RNA病毒科感染/病毒学 RNA 信使/代谢 鼻病毒属/代谢 鼻病毒属/致病力 鼻病毒属/生理学 转录因子AP-1/代谢 转录 遗传 病毒复制 人类 

摘      要：Virus infections, the majority of which are rhinovirus infections, are the major cause of asthma exacerbations. Treatment is unsatisfactory, and the pathogenesis unclear. Lower airway lymphocyte and eosinophil recruitment and activation are strongly implicated, but the mechanisms regulating these processes are unknown. Intercellular adhesion molecule-1 (ICAM-1) has a central role in inflammatory cell recruitment to the airways in asthma and is the cellular receptor for 90% of rhinoviruses. We hypothesized that rhinovirus infection of lower airway epithelium might induce ICARI-1 expression, promoting both inflammatory cell infiltration and rhinovirus infection. We therefore investigated the effect of rhinovirus infection on respiratory epithelial cell ICAM-1 expression and regulation to identify new targets for treatment of virus-induced asthma exacerbations. We observed that rhinovirus infection of primary bronchial epithelial cells and the A549 respiratory epithelial cell line increased ICAM-1 cell surface expression over 12- and 3-fold, respectively. We then investigated the mechanisms of this induction in A549 cells and observed rhinovirus-induction of ICAM-1 promoter activity and ICAM-1 mRNA transcription. Rhinovirus induction of ICAM-1 promoter activity was critically dependent upon up-regulation of NP-kappa B proteins binding to the -187/-178 NF-kappa B binding site on the ICAM-1 promoter. The principal components of the rhinovirus-induced binding proteins were NF-kappa B p65 homo- or heterodimers. These studies identify ICAM-1 and NF-kappa B as new targets for the development of therapeutic interventions for virus-induced asthma exacerbations.