NEUTROPHIL ELASTASE IN RESPIRATORY EPITHELIAL LINING FLUID OF INDIVIDUALS WITH CYSTIC-FIBROSIS INDUCES INTERLEUKIN-8 GENE-EXPRESSION IN A HUMAN BRONCHIAL EPITHELIAL-CELL LINE
NEUTROPHIL ELASTASE IN RESPIRATORY EPITHELIAL LINING FLUID OF INDIVIDUALS WITH CYSTIC-FIBROSIS INDUCES INTERLEUKIN-8 GENE-EXPRESSION IN A HUMAN BRONCHIAL EPITHELIAL-CELL LINE
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DOI：
10.1172/jci115738
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发表时间：
1992-05-01
影响因子：
15.9
通讯作者：
CRYSTAL, RG
中科院分区：
文献类型：
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作者：
NAKAMURA, H;YOSHIMURA, K;CRYSTAL, RG
囊性纤维化（CF）的呼吸系统表现以嗜酸性粒细胞为主的气道炎症为特征。由于各种炎症刺激能够诱导支气管上皮细胞表达IL-8基因，IL-8是一种吸引和激活中性粒细胞的细胞因子，CF个体的呼吸道上皮衬里液（ELF）中的介质可能诱导上皮细胞产生IL-8，从而将中性粒细胞募集到气道。BET-1A人支气管上皮细胞在静止或与正常ELF孵育时显示很少的IL-8基因表达，但与CF ELF孵育后，观察到IL-8转录水平显著增加。CF ELF含有高水平的中性粒细胞弹性蛋白酶（NE），并且各种丝氨酸蛋白酶抑制剂阻止CF ELF诱导BET-1A细胞中IL-8基因的表达，表明NE是CF ELF中IL-8产生的主导诱导剂。加入纯化的NE引起BET-1A细胞增加IL-8基因转录，mRNA转录物积累，并释放IL-8样中性粒细胞趋化活性。这些观察结果表明CF支气管表面上的自我持续的炎症过程，其中由中性粒细胞释放的NE诱导支气管上皮分泌IL-8，这进而将额外的中性粒细胞募集到支气管表面。
The respiratory manifestations of cystic fibrosis (CF) are characterized by neutrophil-dominated airway inflammation. Since a variety of inflammatory stimuli are capable of inducing bronchial epithelial cells to express the gene for IL-8, a cytokine that attracts and activates neutrophils, mediators in respiratory epithelial lining fluid (ELF) of CF individuals might induce IL-8 production by epithelial cells, thus recruiting neutrophils to the airways. BET-1A human bronchial epithelial cells at rest or incubated with normal ELF showed little IL-8 gene expression, but after incubation with CF ELF, a marked increase in IL-8 transcript levels was observed. CF ELF contained high levels of neutrophil elastase (NE) and various serine protease inhibitors prevented CF ELF from inducing IL-8 gene expression in BET-1A cells, suggesting that NE was the dominant inducer for IL-8 production in CF ELF. The addition of purified NE caused BET-1A cells to increase IL-8 gene transcription with accumulation of mRNA transcripts and to release IL-8-like neutrophil chemotactic activity. These observations suggest a self-perpetuating inflammatory process on the CF bronchial surface where NE released by neutrophils induced the bronchial epithelium to secrete IL-8, which in turn recruits additional neutrophils to the bronchial surface.