Induction of interferon system genes in Atlantic salmon by the imidazoquinoline S-27609, a ligand for Toll-like receptor 7.
Imidazoquinolines represented by imiquimod and its derivative S-27609, have previously been shown to have potent antiviral and antitumor activity in several mammalian models. Much of the antiviral properties of imidazoquinolines have been ascribed to induction of IFN-alpha in peripheral blood mononuclear cells most notably plasmacytoid dendritic cells. Toll-like receptor (TLR) 7 has been identified as the receptor for imiquimod and S-27609 in mammals. In this work we show that S-27609 induces expression of IFN-alpha1/alpha2, Mx, ISG15 and IFN-gamma in organs of Atlantic salmon, which suggests that salmon responds to S-27609 through a TLR7-like receptor. The kinetics of gene expression in liver and head kidney induced by S-27609 was compared with that induced by the double-stranded RNA poly I:C, which is a ligand for TLR3 and the RNA helicase MDA5. In liver, S-27609 and poly I:C both induced transcripts for IFN-alpha1/alpha2, Mx and ISG15 with a peak at about 24h. In head kidney, poly I:C induced IFN-alpha1/alpha2 and Mx with one peak at about 24h. In contrast, S-27609 induced a biphasic increase of IFN-alpha1/alpha2 and Mx transcripts in head kidney with a minor peak at 14-24h and another increase starting at 72h. The other major difference in gene induction by the two stimulants was that S-27609 induced much lower levels of IFN-alpha1/alpha2 than poly I:C during the early time stages (14-48h) both in liver and head kidney. The difference in induction of IFN-alpha1/alpha2 by S-27609 and poly I:C may be a consequence of different cell targets for the two stimulants where S-27609 primarily induces IFNs through immune cells whereas poly I:C induces IFNs in most nucleated cells.
Kileng
Øyvind
Ø
Department of Marine Biotechnology, Norwegian College of Fishery Science, University of Tromsø, Breivika, N-9037 Tromsø, Norway.
Albuquerque
Artur
A
Robertsen
Børre
B
D000634:Aminoquinolines / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D015151:Immunoblotting; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007372:Interferons / Q000235:genetics* / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects; D008024:Ligands; D008099:Liver / Q000187:drug effects; D064547:Myxovirus Resistance Proteins; D011070:Poly I-C / Q000494:pharmacology; D020317:Salmo salar / Q000235:genetics* / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000378:metabolism*; D015533:Transcriptional Activation
C095471:4-amino-alpha,alpha,2-trimethyl-1H-imidazo(4,5-c)quinoline-1-ethanol; D000634:Aminoquinolines; D016898:Interferon-alpha; D008024:Ligands; D064547:Myxovirus Resistance Proteins; D051199:Toll-Like Receptor 7; D007371:Interferon-gamma; D007372:Interferons; D019204:GTP-Binding Proteins; D011070:Poly I-C