title: n-3 Fatty acids regulate the inflammatory-state related genes in the lung epithelial cells exposed to polycyclic aromatic hydrocarbons.
abstract: BACKGROUND
  Chronic airway inflammation is coordinated by a complex of inflammatory mediators, including eicosanoids. The aim of this study was to evaluate the impact of polycyclic aromatic hydrocarbons (PAHs) on the human lung epithelial carcinoma A549 cells supplemented with docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids.
  
  
  METHODS
  We analyzed the influence of DHA, EPA and/or benzo(a)pyrene (BaP), chrysene (Chr), fluoranthene (Flu) and benzo(a)anthracene (Baa) treatment on the fatty acids (FAs) profile and the formation of isoprostanes. We studied the cyclooxygenase-2, FP-receptor, peroxisome proliferator-activated receptors PPARδ and PPARγ, transcription factor NF-кB p50 and p65 expression by Western blot, phospholipase A2 (cPLA2) activity, as well as aryl hydrocarbon receptor (AHR), cytochrome P450 (CYP1A1), phospholipase A2 (PLA2G4A) and prostaglandin synthase 2 (PTGS2) gene expression by qRT-PCR.
  
  
  RESULTS
  DHA or EPA supplementation and BaP or Baa treatment resulted in a higher level of PGF3α. COX-2 expression was decreased while PPARδ expression and cPLA2 activity was increased after fatty acid supplementation and PAHs treatment. DHA and EPA up-regulated AHR and PLA2G4A genes.
  
  
  CONCLUSIONS
  Supplementation with n-3 FAs resulted in changes of inflammatory-state related genes in the lung epithelial cells exposed to PAHs. The altered profile of lipid mediators from n-3 FA as well as repression of the COX-2 protein by n-3 PUFAs in A549 cells incubated with PAHs suggests anti-inflammatory and pro-resolving properties of DHA and EPA. It remains to be shown whether these pleiotropic and protective actions of n-3 FAs contribute to fish oil's therapeutic effect in asthma.
authors.affiliation: Department of Radioligands, Faculty of Pharmacy, Jagiellonian University, Medical College, Kraków, Poland. Electronic address: jargasinska@cm-uj.krakow.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Gdula-Argasińska
authors.affiliation: Department of Infectious Diseases, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Czepiel
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland; Center for Medical Genomics-OMICRON, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Totoń-Żurańska
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland; Center for Medical Genomics-OMICRON, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Wołkow
authors.affiliation: Department of Radioligands, Faculty of Pharmacy, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Librowski
authors.affiliation: Faculty of Management, AGH University of Science and Technology, Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Czapkiewicz
authors.affiliation: Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: William
authors.initials: W
authors.lastname: Perucki
authors.affiliation: Laboratory of Forensic Chemistry, Faculty of Chemistry, Jagiellonian University in Kraków, Kraków, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Woźniakiewicz
authors.affiliation: Laboratory of Forensic Chemistry, Faculty of Chemistry, Jagiellonian University in Kraków, Kraków, Poland.
authors.forename: Aneta
authors.initials: A
authors.lastname: Woźniakiewicz
mesh_terms: D000072283:A549 Cells; D001564:Benzo(a)pyrene / Q000494:pharmacology; D045744:Cell Line, Tumor; D002911:Chrysenes / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005449:Fluorenes / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D054513:Group IV Phospholipases A2 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000494:pharmacology*; D011460:Prostaglandins F / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism
chemical_list: D002911:Chrysenes; D015525:Fatty Acids, Omega-3; D005449:Fluorenes; D016328:NF-kappa B; D047495:PPAR gamma; D011084:Polycyclic Aromatic Hydrocarbons; D011460:Prostaglandins F; D018336:Receptors, Aryl Hydrocarbon; C031180:chrysene; D004281:Docosahexaenoic Acids; D001564:Benzo(a)pyrene; C007738:fluoranthene; C034238:prostaglandin F3alpha; D015118:Eicosapentaenoic Acid; D019363:Cytochrome P-450 CYP1A1; D051546:Cyclooxygenase 2; D054513:Group IV Phospholipases A2; C516389:PLA2G4A protein, human
keywords: A549 cells; Gene expression; Isoprostanes; Polycyclic aromatic hydrocarbons; n-3 Fatty acids