title: β-naphthoflavone interferes with cyp1c1, cox2 and IL-8 gene transcription and leukotriene B4 secretion in Atlantic cod (Gadus morhua) head kidney cells during inflammation.
abstract: The objective of this study was to evaluate how β-naphthoflavone interacts with lipopolysaccharide (LPS) and polyinosinic acid: polycytidylic acid (poly I: C) induced innate immune parameters as well as phase I and phase II detoxification enzymes in head kidney cells isolated from Atlantic cod. β-naphthoflavone is a pure agonist of aryl hydrocarbon receptor (AhR) while LPS and poly I: C are not. β-naphthoflavone was added to head kidney leukocytes alone or together with LPS or poly I: C and the responses were evaluated in terms of protein and gene expression. The results showed that β-naphthoflavone (25 nM), with and without LPS, significantly induced cytochrome P450 (cyp1c) transcription in cod head kidney cells. β-naphthoflavone (100 nM) in the presence of the virus mimic, poly I: C, also increased cyp1c1transcription. LPS induced cyp1c1, cyclooxygenase 2 (cox2), interleukin 1β (IL-1β), interleukin 6 (IL-6) and interleukin 8 (IL-8) transcription, genes that were not affected by the tested β-naphthoflavone concentrations alone. However, β-naphthoflavone (25 and 50 nM) strengthened LPS induced cox2 and IL-8 transcription. Cod head kidney cells exposed to β-naphthoflavone concentrations ranging from 25 to 100 nM, with and without LPS or poly I: C, expressed AhR protein. LPS or β-naphthoflavone (5-50 nM) significantly induced leukotriene B4 (LTB4) secretion compared to control. In conclusion, this study suggests that β-naphthoflavone could interfere with LPS induced immune cell signaling in cod head kidney cells.
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P. B. 2029 Nordnes, 5817, Bergen, Norway. Electronic address: eho@nifes.no.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Holen
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P. B. 2029 Nordnes, 5817, Bergen, Norway.
authors.forename: Pål A
authors.initials: PA
authors.lastname: Olsvik
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000633:toxicity*; D029941:Fish Proteins / Q000235:genetics* / Q000378:metabolism; D048389:Gadus morhua / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D060226:Head Kidney / Q000187:drug effects / Q000378:metabolism; D007113:Immunity, Innate; D007249:Inflammation; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D050216:Metabolic Detoxication, Phase I; D050217:Metabolic Detoxication, Phase II; D011070:Poly I-C / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects*; D019324:beta-Naphthoflavone / Q000633:toxicity*
chemical_list: D004791:Enzyme Inhibitors; D029941:Fish Proteins; D008070:Lipopolysaccharides; D007975:Leukotriene B4; D019324:beta-Naphthoflavone; D011070:Poly I-C
keywords: Cod head kidney cells; LPS; LTB4; cox2,IL-8; cyp1c1; β -naphthoflavone