title: Nonylphenol induces bronchial epithelial apoptosis via Fas-mediated pathway and stimulates bronchial epithelium to secrete IL-6 and IL-8, causing bronchial smooth muscle proliferation and migration.
abstract: Features of airway remodelling have been described using tissue obtained from fatal cases of asthma and bronchial biopsies from mildly, moderately and severely asthmatic patients. Epithelial detachment and smooth muscle mass enhancement are common features of asthmatic bronchial tissue. This study is the first to investigate the inhibitory effect of nonylphenol (NP) on human bronchial epithelial cell lines BEAS-2B and HBE135-E6E7 (HBE). The results show that NP inhibits bronchial epithelial proliferation via the Fas/Fas ligand apoptotic system. We also treated BEAS-2B and HBE with NP and harvested the condition medium (CM), which was then added to bronchial smooth muscle cells (BSMC). Cultures of BSMC with NP-BEAS-2B-CM and NP-HBE-CM increased BSMC proliferation and migration. Exposure of BEAS-2B and HBE to NP caused epithelial cells to produce inflammatory cytokines IL-6 and IL-8, which subsequently induced BSMC proliferation and migration. Depleting both IL-6 and IL-8 completely reversed the effect of NP-BEAS-2B-CM- and NP-HBE-CM-mediated BSMC proliferation and migration, suggesting that this effect is a synergistic influence of IL-6 and IL-8. This study is the first to demonstrate that NP not only induces bronchial epithelial apoptosis via the Fas-mediated pathway but also stimulates the bronchial epithelium to secrete IL-6 and IL-8, which cause bronchial smooth muscle proliferation and migration - major features in asthma remodelling.
authors.affiliation: Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanCenter of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanDivision of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Po-Lin
authors.initials: PL
authors.lastname: Kuo
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Hsu
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Chi-Tun
authors.initials: CT
authors.lastname: Lien
authors.forename: Ming-Shyan
authors.initials: MS
authors.lastname: Huang
authors.forename: Ying-Chin
authors.initials: YC
authors.lastname: Ko
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D053222:Fas Ligand Protein / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D015850:Interleukin-6; D016209:Interleukin-8; D010636:Phenols; C025256:nonylphenol; C505530:CASP8 protein, human; D053181:Caspase 8