Division of Pediatric Pulmonary Medicine, Department of Pediatrics, University of California, San Francisco School of Medicine , San Francisco, CA , USA .
Inhal Toxicol. 2013 Oct;25(12):653-60. doi: 10.3109/08958378.2013.827283.
Chronic exposure to ambient particulate matter pollution during childhood is associated with decreased lung function growth and increased prevalence of reported respiratory symptoms. The role of airway epithelium-derived factors has not been well determined.
To determine if urban particulate matter (UPM) stimulates production of vascular endothelial growth factor (VEGF) and transforming growth factor-β2 (TGF-β2), and gene expression of mucin 5AC (MUC5AC) and interleukin-(IL)-8 by primary airway epithelial cells (AECs) obtained from carefully phenotyped healthy and atopic asthmatic school-aged children.
Primary AECs from 9 healthy and 14 asthmatic children were differentiated in air--liquid interface (ALI) culture. The apical surface was exposed to UPM suspension or phosphate buffered saline (PBS) vehicle control for 96 h. VEGF and TGF-β2 concentrations in cell media at baseline, 48 and 96 h were measured via ELISA. MUC5AC and IL-8 expression by AECs at 96 h was measured via quantitative polymerase chain reaction.
Baseline concentrations of VEGF, but not TGF-β2, were significantly higher in asthmatic versus healthy cultures. UPM stimulated production of VEGF, but not TGF-β2, at 48 and 96 h; the magnitude of change was comparable across groups. At 96 h there was greater MUC5AC and IL-8 expression by UPM exposed compared to PBS exposed AECs.
Induction of the pro-remodeling cytokine VEGF may be a potential mechanism by which UPM influences lung function growth in children irrespective of asthma status. Respiratory morbidity associated with UPM exposure in children may be related to increased expression of MUC5AC and IL-8.
儿童时期慢性暴露于环境细颗粒物污染与肺功能生长下降和报告的呼吸道症状患病率增加有关。气道上皮细胞衍生因子的作用尚未得到很好的确定。
确定城市颗粒物 (UPM) 是否刺激从精心表型的健康和特应性哮喘学龄儿童中获得的原代气道上皮细胞 (AEC) 产生血管内皮生长因子 (VEGF) 和转化生长因子-β2 (TGF-β2)，以及粘蛋白 5AC (MUC5AC) 和白细胞介素-(IL)-8 的基因表达。
在气液界面 (ALI) 培养中将 9 名健康和 14 名哮喘儿童的原代 AEC 分化。将气道上皮的顶表面暴露于 UPM 悬浮液或磷酸盐缓冲盐水 (PBS) 载体对照 96 小时。通过 ELISA 在基线、48 和 96 小时测量细胞培养基中 VEGF 和 TGF-β2 的浓度。通过定量聚合酶链反应在 96 小时测量 AEC 中 MUC5AC 和 IL-8 的表达。
与健康培养物相比，哮喘培养物中 VEGF 的基线浓度，但不是 TGF-β2 的基线浓度明显更高。UPM 在 48 和 96 小时刺激 VEGF 的产生，但不刺激 TGF-β2 的产生；各组之间变化的幅度相当。在 96 小时时，与 PBS 暴露的 AEC 相比，暴露于 UPM 的 AEC 中 MUC5AC 和 IL-8 的表达更高。
促重塑细胞因子 VEGF 的诱导可能是 UPM 影响儿童肺功能生长的潜在机制，而与哮喘状态无关。儿童 UPM 暴露相关的呼吸道发病率可能与 MUC5AC 和 IL-8 的表达增加有关。
