Pseudomonas aeruginosa induces MUC5AC production via epidermal growth factor receptor
Pseudomonas aeruginosa induces MUC5AC production via epidermal growth factor receptor
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DOI：
10.1183/09031936.02.00001402
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发表时间：
2002-11-01
影响因子：
24.3
通讯作者：
Nadel, JA
中科院分区：
文献类型：
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作者：
Kohri, K;Ueki, IF;Nadel, JA
与铜绿假单胞菌（PA）感染相关的分泌过多疾病的特征在于杯状细胞增加和粘蛋白产生增加。最近，表皮生长因子受体（EGFR）信号级联被证明是一种常见的途径，通过它许多刺激诱导气道中的粘蛋白MUC 5AC表达分化为杯状细胞表型。本研究观察PA产物是否诱导EGFR表达和活化，从而导致粘蛋白MUC 5AC的产生。用酶联免疫吸附试验、原位杂交和免疫印迹法检测MUC 5AC蛋白的产生、MUC 5AC和EGFR信使核糖核酸（mRNA）的表达、磷酸化EGFR和磷酸化p44/42丝裂原活化蛋白激酶（MAPK）。用选择性EGFR酪氨酸激酶抑制剂预处理可完全抑制MUC 5AC mRNA和蛋白表达以及EGFR和p44/42 MAPK磷酸化。用选择性MAPK激酶抑制剂预处理可阻止MUC 5AC的产生和p44/42 MAPK磷酸化，但不能阻止EGFR磷酸化。作者得出结论，PA产物通过表皮生长因子受体的表达和激活诱导人气道上皮细胞中粘蛋白MUC 5AC的产生。
Hypersecretory disease associated with Pseudomonas aeruginosa (PA) infections is characterised by increased goblet cells and increased mucin production. Recently, an epidermal growth factor receptor (EGFR) signalling cascade was shown to be a common pathway through which many stimuli induce mucin MUC5AC expression in airways by differentiation to a goblet cell phenotype. This study looked at whether PA products induce EGFR expression and activation and thus result in mucin MUC5AC production.Human airway epithelial (NCI-H292) cells were stimulated with PA culture supernatant (Sup). MUC5AC protein production, MUC5AC and EGFR messenger ribonucleic acid (mRNA) expression, and phosphorylated EGFR and phosphorylated p44/42 mitogen-activated protein kinase (MAPK) were all examined using enzyme-linked immunosorbent assay, by in situ hybridisation and by immunoblotting.PA Sup induced MUC5AC mRNA and subsequent protein expression, EGFR and p44/42 MAPK phosphorylation and EGFR mRNA expression. Induction of MUC5AC mRNA and protein expression and EGFR and p44/42 MAPK phosphorylation were inhibited completely by pretreatment with a selective EGFR tyrosine kinase inhibitor. Pretreatment with a selective inhibitor of MAPK kinase prevented MUC5AC production and p44/42 MAPK phosphorylation but not EGFR phosphorylation.The authors conclude that PA products induce mucin MUC5AC production in human airway epithelial cells via the expression and activation of epidermal growth factor receptor.