title: Gene and protein responses of human lung tissue explants exposed to ambient particulate matter of different sizes.
abstract: BACKGROUND
  Exposure to ambient particulate air pollution is associated with increased cardiovascular and respiratory morbidity and mortality. It is necessary to understand causal pathways driving the observed health effects, particularly if they are differentially associated with particle size.
  
  
  OBJECTIVE
  To investigate the effect of different size ranges of ambient particulate matter (PM) on gene and protein expression in an in vitro model.
  
  
  METHODS
  Normal human tracheobronchial epithelium (NHTBE) three-dimensional cell constructs were exposed for 24 h to washed ambient PM of different sizes (size 1: 7-615 nm; size 2: 616 nm-2.39 µm; size 3: 2.4-10 µm) collected from a residential street. A human stress and toxicity PCR array was used to investigate gene expression and iTRAQ was used to perform quantitative proteomics.
  
  
  RESULTS
  Eighteen different genes of the 84 on the PCR array were significantly dysregulated. Treatment with size 2 PM resulted in the greatest number of genes with altered expression, followed by size 1 and lastly size 3. ITRAQ identified 317 proteins, revealing 20 that were differentially expressed. Enrichment for gene ontology classification revealed potential changes to various pathways.
  
  
  CONCLUSIONS
  Different size fractions of ambient PM are associated with dysregulatory effects on the cellular proteome and on stress and toxicity genes of NHTBE cells. This approach not only provides an investigative tool to identify possible causal pathways but also permits the relationship between particle size and responses to be explored.
authors.affiliation: Department of Primary Care and Public Health, Neuadd Meirionnydd, School of Medicine, Heath Park, Cardiff, UK. hoogendoornb@cardiff.ac.uk
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Hoogendoorn
authors.forename: Kelly
authors.initials: K
authors.lastname: Berube
authors.forename: Clive
authors.initials: C
authors.lastname: Gregory
authors.forename: Tim
authors.initials: T
authors.lastname: Jones
authors.forename: Keith
authors.initials: K
authors.lastname: Sexton
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Ian A
authors.initials: IA
authors.lastname: Brewis
authors.forename: Alexander
authors.initials: A
authors.lastname: Murison
authors.forename: Robert
authors.initials: R
authors.lastname: Arthur
authors.forename: Heather
authors.initials: H
authors.lastname: Price
authors.forename: Huw
authors.initials: H
authors.lastname: Morgan
authors.forename: Ian P
authors.initials: IP
authors.lastname: Matthews
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002460:Cell Line; D017097:Electric Impedance; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D023281:Genomics / Q000379:methods; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D025941:Protein Interaction Mapping; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D052638:Particulate Matter; D011506:Proteins; D000255:Adenosine Triphosphate