Chronic exposure to particulate pollution is suspected to exacerbate inflammatory respiratory diseases such as asthma characterized by an airway remodelling involving fibrosis. Our study aims to investigate whether the secretome from human bronchial epithelial (HBE) cells exposed to fine particulate matter (PM) induces fibroblast proliferation. Primary HBE cells grown on air liquid interface were repeatedly exposed to fine PM at 5 and 10 μg/cm2 (four treatments, 48 hours apart) and maintained in culture for five weeks. Collected basolateral culture medium was used as a conditioned medium for the subsequent treatment of fibroblasts. We observed that the conditioned medium collected from HBE cells treated with fine PM increased the growth rate of fibroblasts compared to the conditioned medium collected from control HBE cells. Fibroblast phenotype assessed by the observation of the vimentin network was well preserved. The mitogenic effect of conditioned medium was reduced in the presence of anti-epidermal growth factor receptor (EGFR), anti-amphiregulin or anti-TGFa, underlining the role of EGFR ligands in fibroblast proliferation. When fibroblasts were co-cultured with HBE cells treated once with fine PM, they exhibited a higher growth rate than fibroblasts co-cultured with non-treated HBE cells. Altogether these data show that the exposure of HBE cells to fine PM induced the production of EGFR ligands in sufficient amount to stimulate fibroblast proliferation providing insight into the role of PM in airway remodelling.
References
[1]
Pascal, M.; Corso, M.; Chanel, O.; Declercq, C.; Badaloni, C.; Cesaroni, G.; Henschel, S.; Meister, K.; Haluza, D.; Martin-Olmedo, P.; Medina, S.; hekom group. Assessing the public health impacts of urban air pollution in 25 European cities: Results of the Aphekom project. Sci. Total Environ. 2013, 449, 390–400, doi:10.1016/j.scitotenv.2013.01.077.
[2]
Holgate, S.T. The sentinel role of the airway epithelium in asthma pathogenesis. Immunol. Rev. 2011, 242, 205–219, doi:10.1111/j.1600-065X.2011.01030.x.
[3]
Blanchet, S.; Ramgolam, K.; Baulig, A.; Marano, F.; Baeza-Squiban, A. Fine particulate matter induces amphiregulin secretion by bronchial epithelial cells. Am. J. Respir. Cell. Mol. Biol. 2004, 30, 421–427, doi:10.1165/rcmb.2003-0281RC.
[4]
Rumelhard, M.; Ramgolam, K.; Hamel, R.; Marano, F.; Baeza-Squiban, A. Expression and role of EGFR ligands induced in airway cells by PM2.5 and its components. Eur. Respir. J. 2007, 30, 1064–1073, doi:10.1183/09031936.00085907.
[5]
Enomoto, Y.; Orihara, K.; Takamasu, T.; Matsuda, A.; Gon, Y.; Saito, H.; Ra, C.; Okayama, Y. Tissue remodeling induced by hypersecreted epidermal growth factor and amphiregulin in the airway after an acute asthma attack. J. Allergy Clin. Immunol. 2009, 124, 913–920, doi:10.1016/j.jaci.2009.08.044.
[6]
Ramgolam, K.; Hamel, R.; Rumelhard, M.; Marano, F.; Baeza-Squiban, A. Autocrine effect of EGFR ligands on the pro-inflammatory response induced by PM(2.5) exposure in human bronchial epithelial cells. Arch. Toxicol. 2012, 86, 1537–1546, doi:10.1007/s00204-012-0863-x.
[7]
Val, S.; Belade, E.; George, I.; Boczkowski, J.; Baeza-Squiban, A. Fine PM induce airway MUC5AC expression through the autocrine effect of amphiregulin. Arch. Toxicol. 2012, 86, 1851–1859, doi:10.1007/s00204-012-0903-6.
[8]
Bonner, J.C. Mesenchymal cell survival in airway and interstitial pulmonary fibrosis. Fibrogenesis Tissue Repair 2010, 3, 1755–1536, doi:10.1186/1755-1536-3-15.
[9]
Wang, S.W.; Oh, C.K.; Cho, S.H.; Hu, G.; Martin, R.; Demissie-Sanders, S.; Li, K.; Moyle, M.; Yao, Z. Amphiregulin expression in human mast cells and its effect on the primary human lung fibroblasts. J. Allergy Clin. Immunol. 2005, 115, 287–294, doi:10.1016/j.jaci.2004.11.037.
[10]
Zhou, Y.; Lee, J.Y.; Lee, C.M.; Cho, W.K.; Kang, M.J.; Koff, J.L.; Yoon, P.O.; Chae, J.; Park, H.O.; Elias, J.A.; Lee, C.G. Amphiregulin, an epidermal growth factor receptor ligand, plays an essential role in the pathogenesis of transforming growth factor-β-induced pulmonary fibrosis. J. Biol. Chem. 2012, 287, 41991–42000, doi:10.1074/jbc.M112.356824.
[11]
Dai, J.; Xie, C.; Vincent, R.; Churg, A. Air pollution particles produce airway wall remodeling in rat tracheal explants. Am. J. Respir Cell. Mol. Biol. 2003, 29, 352–358, doi:10.1165/rcmb.2002-0318OC.
[12]
Boublil, L.; Assémat, E.; Borot, M.C.; Boland, S.; Martinon, L.; Sciare, J.; Baeza-Squiban, A. Development of repeated exposure protocol of human bronchial epithelium in vitro to study the long-term effects of atmospheric particles. Toxicol. In Vitro 2013, 27, 533–542, doi:10.1016/j.tiv.2012.11.008.
[13]
Kendall, M.; Holgate, S. Health impact and toxicological effects of nanomaterials in the lung. Respirology 2012, 17, 743–758, doi:10.1111/j.1440-1843.2012.02171.x.
[14]
Ramgolam, K.; Favez, O.; Cachier, H.; Gaudichet, A.; Marano, F.; Martinon, L.; Baeza-Squiban, A. Size-partitioning of an urban aerosol to identify particle determinants involved in the proinflammatory response induced in airway epithelial cells. Part Fibre Toxicol. 2009, 6, 10, doi:10.1186/1743-8977-6-10.
[15]
Val, S.; Martinon, L.; Cachier, H.; Yahyaoui, A.; Marfaing, H.; Baeza-Squiban, A. Role of size and composition of traffic and agricultural aerosols in the molecular responses triggered in airway epithelial cells. Inhal. Toxicol. 2011, 23, 627–640, doi:10.3109/08958378.2011.599445.
[16]
Val, S.; Liousse, C.; Doumbia, E.H.; Galy-Lacaux, C.; Cachier, H.; Marchand, N.; Badel, A.; Gardrat, E.; Sylvestre, A.; Baeza-Squiban, A. Physico-chemical characterization of African urban aerosols (Bamako in Mali and Dakar in Senegal) and their toxic effects in human bronchial epithelial cells: Description of a worrying situation. Part Fibre Toxicol. 2013, 10, 10, doi:10.1186/1743-8977-10-10.
[17]
Choi, H.S.; Ashitate, Y.; Lee, J.H.; Kim, S.H.; Matsui, A.; Insin, N.; Bawendi, M.G.; Semmler-Behnke, M.; Frangioni, J.V.; Tsuda, A. Rapidtranslocationof nanoparticles from the lung airspaces to the body. Nat. Biotechnol. 2010, 28, 1300–1303, doi:10.1038/nbt.1696.
[18]
George, I.; Vranic, A.; Boland, S.; Borot, M.C.; Marano, F.; Baeza-Squiban, A. Translocation of SiO2-NPs across in vitro human bronchial epithelial monolayer. J. Physics 2013. in press.
[19]
Hardie, W.D.; Le Cras, T.D.; Jiang, K.; Tichelaar, J.W.; Azhar, M.; Korfhagen, T.R. Conditional expression of transforming growth factor-alpha in adult mouse lung causes pulmonary fibrosis. Am. J. Physiol. Lung Cell Mol. Physiol. 2004, 286, L741–L749.
