Th2 cytokines exert a dominant influence on epithelial cell expression of the major group human rhinovirus receptor, ICAM-1
Th2 cytokines exert a dominant influence on epithelial cell expression of the major group human rhinovirus receptor, ICAM-1
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DOI：
10.1183/09031936.98.12030619
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发表时间：
1998-09-01
影响因子：
24.3
通讯作者：
Spiteri, MA
中科院分区：
文献类型：
--
作者：
Bianco, A;Sethi, SK;Spiteri, MA
细胞间粘附分子 (ICAM)-1 是人鼻病毒 (HRV) 附着和免疫效应细胞动员中重要的细胞受体。因此，上皮细胞 (EC) 的 ICAM-1 表达水平在病毒结合、宿主感染和随后的炎症事件的复杂生物学现象中起着至关重要的作用。由于辅助性 T (Th)2 淋巴细胞在哮喘气道内占主导地位，因此评估了 Th2 相关介质在调节未感染和HRV感染的EC上ICAM-1的表达，H292 EC在体外培养，用不同浓度的白细胞介素(IL)-4、IL-5、IL-10和IL-13培养24小时，然后用活HRV-14感染。通过免疫细胞化学评估表面 ICAM-1 表达。HRV-14 感染导致 ICAM-1 表达增加两倍。 IL-4、IL-5、IL-10和IL-13使未感染细胞的ICAM-1表达增加了2.7-5.1倍，并导致感染细胞中的ICAM-1表达比HRV感染本身诱导的表达进一步增加大约两倍。干扰素-γ 与每种 Th2 相关细胞因子联合仅轻微降低，但并未覆盖未感染和病毒感染的 EC 上 Th2 诱导的 ICAM-1 表达水平。这些数据表明，Th2 相关细胞因子对细胞间粘附分子-1 表达和感染性病毒恢复的影响比 Th1 相关细胞因子（如干扰素-γ）的影响占主导地位。由于特应性哮喘的气道粘膜主要被 Th2 淋巴细胞浸润，这些结果可以解释哮喘患者对人鼻病毒感染的易感性增加以及相关的哮喘症状恶化。
Intercellular adhesion molecule (ICAM)-1 is a cell receptor important in both human rhinovirus (HRV) attachment and immune effector cell mobilization, The level of expression of ICAM-1 by epithelial cells (EC) therefore plays a crucial role in the intricate biological phenomena underlying viral binding, host infection and consequent inflammatory events.As T-helper (Th)2 lymphocytes predominate within the asthmatic airway, the influence was evaluated of Th2-associated mediators in the modulation of ICAM-1 expression on uninfected and HRV-infected EC, H292 EC were cultured in vitro, with varying concentrations of interleukin (IL)-4, IL-5, IL-10 and IL-13 for 24 h and then infected with live HRV-14. Surface ICAM-1 expression was assessed by immunocytochemistry.Infection with HRV-14 resulted in a twofold increase in ICAM-1 expression. IL-4, IL-5, IL-10 and IL-13 produced a 2.7-5.1-fold enhancement of ICAM-1 expression of uninfected cells and caused approximately a further twofold increase in infected cells over the expression induced by HRV infection itself. Interferon-gamma in combination with each Th2-associated cytokine only slightly reduced, but did not override, the Th2-induced level of ICAM-1 expression on both uninfected and virus-infected EC,These data suggest that the effects of Th2-associated cytokines on intercellular adhesion molecule-1 expression and recovery of infectious virus are dominant over the effects of the Th1-associated cytokines such as interferon-gamma. Since the airway mucosa in atopic asthma is predominantly infiltrated by Th2 lymphocytes, these results could explain both the increased susceptibility to human rhinovirus infection in asthmatic patients and the associated exacerbation of asthma symptoms.