title: Lung mucin production is stimulated by the air pollutant residual oil fly ash.
abstract: Human and animal exposure to particulate air pollution is correlated with airway mucus hypersecretion and increased susceptibility to infection. Seeking clues to the mechanisms underlying this pathology, we examined the effect of the particulate air pollutant residual oil fly ash (ROFA) on production of the major component of mucus, mucin, and the major antibacterial protein of the respiratory tract, lysozyme. We found that following in vitro exposure to ROFA, epithelial cells showed an increase in mucin (MUC5AC) and lysozyme (LYS) steady state mRNA. This upregulation was controlled at least partly at the level of transcription as shown by reporter assays. Experiments testing the ability of the major components of ROFA to mimic these effects showed that vanadium, a metal making up 18.8% by weight, accounted for the bulk of the response. A screen of signaling inhibitors showed that MUC5AC and LYS induction by ROFA are mediated by dissimilar signaling pathways, both of which are, however, phosphotyrosine dependent. Recognizing that the ROFA constituent vanadium is a potent tyrosine phosphatase inhibitor and that mucin induction by pathogens is phophotyrosine dependent, we suggest that vanadium-containing air pollutants trigger disease-like conditions by unmasking phosphorylation-dependent pathogen resistance pathways.
authors.affiliation: Department of Anatomy and Cardiovascular Research Institute, University of California, San Francisco 94143, USA.
authors.forename: M
authors.initials: M
authors.lastname: Longphre
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: E
authors.initials: E
authors.lastname: Matovinovic
authors.forename: M
authors.initials: M
authors.lastname: Gallup
authors.forename: J M
authors.initials: JM
authors.lastname: Samet
authors.forename: C B
authors.initials: CB
authors.lastname: Basbaum
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects; D002460:Cell Line; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D005648:Fuel Oils / Q000633:toxicity*; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008175:Lung Neoplasms; D009077:Mucins / Q000096:biosynthesis*; D010316:Particle Size; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014639:Vanadium / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D005648:Fuel Oils; D009077:Mucins; D012333:RNA, Messenger; D014639:Vanadium