AIRWAY EPITHELIAL-CELL EXPRESSION OF INTERLEUKIN-6 IN TRANSGENIC MICE - UNCOUPLING OF AIRWAY INFLAMMATION AND BRONCHIAL HYPERREACTIVITY
AIRWAY EPITHELIAL-CELL EXPRESSION OF INTERLEUKIN-6 IN TRANSGENIC MICE - UNCOUPLING OF AIRWAY INFLAMMATION AND BRONCHIAL HYPERREACTIVITY
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DOI：
10.1172/jci117556
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发表时间：
1994-11-01
影响因子：
15.9
通讯作者：
FLAVELL, RA
中科院分区：
文献类型：
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作者：
DICOSMO, BF;GEBA, GP;FLAVELL, RA
我们生产了在气道上皮细胞中过表达人IL-6的转基因小鼠。转基因小鼠在大中型气道附近出现单核细胞浸润。免疫组化显示这些细胞主要是CD 4（+）细胞、MHC II类细胞和B220（+）细胞。转基因小鼠和非转基因小鼠具有相似的基线呼吸系统阻力（9周龄时0.47+/-0.06 vs 0.43+/-0.04 cmH 2 O/ml/s，P = NS; 17周龄时0.45+/-0.07 vs 0.43+/-0.09 cmH 2 O/ml/s，P = NS）。然而，与非转基因同窝小鼠相比，转基因小鼠需要显著更高的乙酰甲胆碱对数剂量才能使呼吸系统阻力增加100%（1.34+/-0.24 vs 0.34+/-0.05 mg/ml，P小于或等于0.01）。我们的结论是，人IL-6在转基因小鼠的气道中的表达导致了围绕大中型气道的CD 4（+）、MHC II类+、B220（+）淋巴细胞浸润，这并不改变基础呼吸阻力，但确实降低了气道对乙酰甲胆碱的反应性。这些发现证明了IL-6诱导的气道淋巴细胞炎症和气道高反应性的解偶联，并表明某些形式的气道炎症可能有助于恢复改变的气道生理学。
We produced transgenic mice which overexpress human IL-6 in the airway epithelial cells. Transgenic mice develop a mononuclear cell infiltrate adjacent to large and mid-sized airways. Immunohistochemistry reveals these cells to be predominantly CD4(+) cells, MHC class II+ cells, and B220(+) cells. Transgenic mice and nontransgenic mice had similar baseline respiratory system resistance (0.47+/-0.06 vs 0.43+/-0.04 cmH(2)O/ml per s at 9 wk of age, P = NS and 0.45+/-0.07 vs 0.43+/-0.09 cmH(2)O/ml per s at 17 wk of age, P = NS). Transgenic mice, however, required a significantly higher log dose of methacholine to produce a 100% increase in respiratory system resistance as compared with nontransgenic littermates (1.34+/-0.24 vs 0.34+/-0.05 mg/ml, P less than or equal to 0.01). We conclude that the expression of human IL-6 in the airways of transgenic mice results in a CD4(+), MHC class II+, B220(+) lymphocytic infiltrate surrounding large and mid-sized airways that does not alter basal respiratory resistance, but does diminish airway reactivity to methacholine. These findings demonstrate an uncoupling of IL-6-induced airway lymphocytic inflammation and airway hyperresponsiveness and suggest that some forms of airway inflammation may serve to restore altered airway physiology.