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IL-13 对儿童哮喘性支气管上皮细胞纤毛黏液分化的影响。

Effects of IL-13 on mucociliary differentiation of pediatric asthmatic bronchial epithelial cells.

机构信息

Centre for Infection and Immunity, Queen's University Belfast, Belfast BT12 6BN, Northern Ireland, United Kingdom.

出版信息

Pediatr Res. 2011 Feb;69(2):95-100. doi: 10.1203/PDR.0b013e318204edb5.

Abstract

Goblet cell hyperplasia (GCH) and decreased ciliated cells are characteristic of asthma. We examined the effects of IL-13 (2 and 20 ng/mL) on in vitro mucociliary differentiation in pediatric bronchial epithelial cells (PBECs) of normal PBEC [PBEC(N)] and asthmatic PBEC [PBEC(A)] children. Markers of differentiation, real-time PCR for MUC5AC, MUC5AC ELISA, and transepithelial electrical resistance (TEER) were assessed. Stimulation with 20 ng/mL IL-13 in PBEC(N) resulted in GCH [20 ng/mL IL-13: mean, 33.8% (SD, 7.2) versus unstimulated: mean, 18.9% (SD, 5.0); p < 0.0001] and decreased ciliated cell number [20 ng/mL IL-13: mean, 8% (SD, 5.6) versus unstimulated: mean, 22.7% (SD,7.6); p < 0.01]. PBEC(N) stimulated with 20 ng/mL IL-13 resulted in >5-fold (SD, 3.2) increase in MUC5AC mRNA expression, p < 0.001, compared with unstimulated PBEC(N). In PBEC(A), GCH was also seen [20 ng/mL IL-13: mean, 44.7% (SD, 16.4) versus unstimulated: mean, 30.4% (SD, 13.9); p < 0.05] with a decreased ciliated cell number [20 ng/mL IL-13: mean, 8.8% (SD, 7.5) versus unstimulated: mean, 16.3% (SD, 4.2); p < 0.001]. We also observed an increase in MUC5AC mRNA expression with 20 ng/mL IL-13 in PBEC(A), p < 0.05. IL-13 drives PBEC(N) toward an asthmatic phenotype and worsens the phenotype in PBEC(A) with reduced ciliated cell numbers and increased goblet cells.

摘要

杯状细胞增生(GCH)和纤毛细胞减少是哮喘的特征。我们研究了白细胞介素-13(2 和 20ng/ml)对正常支气管上皮细胞(PBEC)和哮喘 PBEC 儿童的体外黏液纤毛分化的影响。用 MUC5AC 的实时 PCR、MUC5AC ELISA 和跨上皮电阻(TEER)评估分化标志物。用 20ng/ml IL-13 刺激 PBEC(N)导致 GCH [20ng/ml IL-13:平均值为 33.8%(标准差,7.2)比未刺激:平均值为 18.9%(标准差,5.0);p<0.0001]和减少纤毛细胞数量[20ng/ml IL-13:平均值为 8%(标准差,5.6)比未刺激:平均值为 22.7%(标准差,7.6);p<0.01]。用 20ng/ml IL-13 刺激的 PBEC(N)导致 MUC5AC mRNA 表达增加 5 倍以上(标准差,3.2),p<0.001,与未刺激的 PBEC(N)相比。在 PBEC(A)中,也观察到 GCH [20ng/ml IL-13:平均值为 44.7%(标准差,16.4)比未刺激:平均值为 30.4%(标准差,13.9);p<0.05]和减少纤毛细胞数量[20ng/ml IL-13:平均值为 8.8%(标准差,7.5)比未刺激:平均值为 16.3%(标准差,4.2);p<0.001]。我们还观察到,在 PBEC(A)中,用 20ng/ml IL-13 刺激 MUC5AC mRNA 表达增加,p<0.05。IL-13 使 PBEC(N)向哮喘表型发展,并使 PBEC(A)的表型恶化,减少纤毛细胞数量,增加杯状细胞。

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