Rumelhard M, Ramgolam K, Hamel R, Marano F, Baeza-Squiban A
Laboratory of Cytophysiology and Cellular Toxicology, Tour 53-54, Case Courrier 7073, University of Paris Diderot-Paris 7, 2 place Jussieu, 75 251 Paris Cedex 05, France.
Eur Respir J. 2007 Dec;30(6):1064-73. doi: 10.1183/09031936.00085907. Epub 2007 Sep 5.
The aim of the current study was to establish the epidermal growth factor receptor (EGFR) ligand expression profile in human airway epithelial cells exposed to either particulate matter (PM) with an aerodynamic diameter <2.5 microm (PM(2.5)) or its components and the involvement of EGFR ligands in PM(2.5)-provoked airway inflammation. EGFR ligand mRNA and protein expression were studied in a human bronchial epithelial cell line and normal nasal cells exposed to noncytotoxic concentrations of PM(2.5) or its components. The autocrine role of EGFR ligands in airway epithelial cell pro-inflammation was determined by adding conditioned media from PM(2.5)-treated cells to fresh cells and measuring the secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF), a pro-inflammatory biomarker. PM(2.5)increased amphiregulin, transforming growth factor-alpha and heparin-binding EGF-like growth factor mRNA expression and protein secretion, with a slight contribution of aqueous metallic compounds and a strong participation of organic components putatively attributed to PM polyaromatic hydrocarbon content. PM(2.5)-induced EGFR ligands were involved in cellular GM-CSF release. The current study revealed upregulation of several epidermal growth factor receptor ligands by airway epithelial cells exposed to particulate matter with an aerodynamic diameter <2.5 microm and their contribution to bronchial epithelial cell granulocyte-macrophage colony-stimulating factor secretion by an autocrine action, suggesting that these ligands could elicit and sustain the particulate matter-induced airway pro-inflammatory response and contribute to bronchial remodelling.
本研究的目的是确定暴露于空气动力学直径小于2.5微米的颗粒物（PM2.5）或其成分的人气道上皮细胞中的表皮生长因子受体（EGFR）配体表达谱，以及EGFR配体在PM2.5诱发的气道炎症中的作用。在人支气管上皮细胞系和暴露于非细胞毒性浓度的PM2.5或其成分的正常鼻细胞中研究了EGFR配体mRNA和蛋白表达。通过将来自PM2.5处理细胞的条件培养基添加到新鲜细胞中并测量促炎生物标志物粒细胞-巨噬细胞集落刺激因子（GM-CSF）的分泌，确定了EGFR配体在气道上皮细胞促炎中的自分泌作用。PM2.5增加了双调蛋白、转化生长因子-α和肝素结合表皮生长因子样生长因子的mRNA表达和蛋白分泌，水性金属化合物的作用较小，而有机成分的作用较强，推测这归因于PM的多环芳烃含量。PM2.5诱导的EGFR配体参与了细胞GM-CSF的释放。本研究揭示了暴露于空气动力学直径小于2.5微米颗粒物的气道上皮细胞中几种表皮生长因子受体配体的上调，以及它们通过自分泌作用对支气管上皮细胞粒细胞-巨噬细胞集落刺激因子分泌的作用，表明这些配体可能引发并维持颗粒物诱导的气道促炎反应，并促进支气管重塑。
