Striz I, Mio T, Adachi Y, Heires P, Robbins R A, Spurzem J R, Illig M J, Romberger D J, Rennard S I
Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198-5300, USA.
Am J Physiol. 1999 Jul;277(1):L58-64. doi: 10.1152/ajplung.1999.277.1.L58.
Interleukin (IL)-4 is thought to contribute to the Th2 type of immune response and hence the development of allergic reactions such as asthma. In asthmatic patients, the airway epithelium expresses increased amounts of the cell surface adhesion molecule intercellular adhesion molecule (ICAM)-1 (CD54). One cytokine capable of inducing ICAM-1 in airway epithelial cells, tumor necrosis factor-alpha (TNF-alpha), is present in asthma. This study evaluated if IL-4 either alone or together with TNF-alpha costimulation might modulate CD54 expression by human bronchial epithelial cells (HBECs). CD54 positivity increased in response to IL-4 (16 +/- 2% positive vs. 3 +/- 1%, P < 0.01); greater induction of CD54 resulted from TNF-alpha (45 +/- 2%, P < 0.001). Costimulation with TNF-alpha plus IL-4 further augmented expression (56 +/- 1%, P < 0.05). Immunoperoxidase results were confirmed by flow cytometry. RT-PCR revealed no increase in ICAM-1 mRNA expression under control conditions or after stimulation with IL-4 alone. TNF-alpha increased IL-4 mRNA, and IL-4 potentiated this. Functionally, IL-4 augmented the adhesion of THP-1 monocyte/macrophage cells to monolayers of HBECs both alone and in the presence of TNF-alpha. We conclude that 1) IL-4 augments epithelial cell ICAM-1 expression, 2) IL-4 potentiates the adhesion of THP-1 monocyte/macrophage cells to epithelial cells, and 3) modulation of epithelial cell ICAM-1 expression by IL-4 may play a role in the immunopathology of bronchial asthma.
白细胞介素（IL）-4被认为有助于Th2型免疫反应，从而导致诸如哮喘等过敏反应的发生。在哮喘患者中，气道上皮细胞表达的细胞表面黏附分子细胞间黏附分子（ICAM）-1（CD54）数量增加。一种能够诱导气道上皮细胞中ICAM-1表达的细胞因子——肿瘤坏死因子-α（TNF-α），在哮喘中也存在。本研究评估了IL-4单独或与TNF-α共刺激是否可能调节人支气管上皮细胞（HBECs）的CD54表达。CD54阳性率在IL-4刺激后升高（16±2%阳性 vs. 3±1%，P<0.01）；TNF-α对CD54的诱导作用更强（45±2%，P<0.001）。TNF-α加IL-4共刺激进一步增强了表达（56±1%，P<0.05）。免疫过氧化物酶结果通过流式细胞术得到证实。RT-PCR显示在对照条件下或单独用IL-4刺激后，ICAM-1 mRNA表达没有增加。TNF-α增加了IL-4 mRNA的表达，而IL-4又增强了这种作用。在功能上，IL-4单独以及在TNF-α存在的情况下，均增强了THP-1单核细胞/巨噬细胞与HBEC单层细胞的黏附。我们得出结论：1）IL-4增强上皮细胞ICAM-1表达；2）IL-4增强THP-1单核细胞/巨噬细胞与上皮细胞的黏附；3）IL-4对上皮细胞ICAM-1表达的调节可能在支气管哮喘的免疫病理学中起作用。
