Functional analysis of carp interferon-y: Evolutionary conservation of classical phagocyte acativation

J.A.J. Arts, E. Tijhaar, M.K. Chadzinska, H.F.J. Savelkoul, B.M.L. Verburg-van Kemenade

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Abstract

In teleost fish two IFN-¿ gene sequences were found for which two phylogenetic clusters can be distinguished. Our previous analysis of expression of these in carp led us to hypothesize that a classical IFN-¿ function is associated with the IFN-¿2 cluster. We investigated the evolutionary conservation of the IFN-¿ function, inducing classical activation of phagocytes, thus skewing towards a Th1-like profile of immune activation. Recombinant proteins for the carp IFN-¿ sequences of both clusters were made and we studied their effects on expression of proinflammatory mediators. Carp IFN-¿2, in contrast to carp IFN-¿1, was powerful in inducing a proinflammatory reaction in phagocytes: a classical synergistic response with lipopolysaccharide was observed for the induction of iNOS expression and NO release, for expression of CXCL9-11-like chemokines and the expression of proinflammatory cytokines IL-1ß, TNFa and the IL-12 subunits p35 and p40. In contrast, like in mammals, the CXCL8-like cytokines are LPS but not IFN-¿ sensitive. These results corroborate an evolutionary conserved nature of IFN-¿ function in lower vertebrates including classical activation of phagocytes
Original languageEnglish
Pages (from-to)793-802
JournalFish and Shellfish Immunology
Volume29
Issue number5
DOIs
Publication statusPublished - 2010

Keywords

  • nitric-oxide synthase
  • common carp
  • ifn-gamma
  • molecular characterization
  • expression analysis
  • messenger-rna
  • tnf-alpha
  • nf-kb
  • macrophages
  • l.

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