Functional analysis of carp interferon-γ: Evolutionary conservation of classical phagocyte activation

In teleost fish two IFN-γ 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-γ function is associated with the IFN-γ2 cluster. We investigated the evolutionary conservatio...

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Bibliographic Details
Published in:Fish & shellfish immunology 2010-11, Vol.29 (5), p.793-802
Main Authors: Arts, J.A.J., Tijhaar, E.J., Chadzinska, M., Savelkoul, H.F.J., Verburg-van Kemenade, B.M.L.
Format: Article
Language:English
Subjects:
Animals
Biological Evolution
Carps - genetics
Carps - immunology
Chemokines - metabolism
Chemotaxis - physiology
Chromatography, Affinity
Classical macrophage activation
CXC chemokines
Cytokines - metabolism
DNA Primers - genetics
DNA, Complementary - genetics
IL-12
IL-1β
iNOS
Interferon-gamma - genetics
Interferon-gamma - immunology
Interferon-γ
Lipopolysaccharides
Nitric Oxide - metabolism
Nitric Oxide Synthase Type II - metabolism
Phagocytes - immunology
Respiratory Burst
Reverse Transcriptase Polymerase Chain Reaction
Teleost
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Summary:In teleost fish two IFN-γ 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-γ function is associated with the IFN-γ2 cluster. We investigated the evolutionary conservation of the IFN-γ function, inducing classical activation of phagocytes, thus skewing towards a Th1-like profile of immune activation. Recombinant proteins for the carp IFN-γ sequences of both clusters were made and we studied their effects on expression of proinflammatory mediators. Carp IFN-γ2, in contrast to carp IFN-γ1, 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-1β, TNFα and the IL-12 subunits p35 and p40. In contrast, like in mammals, the CXCL8-like cytokines are LPS but not IFN-γ sensitive. These results corroborate an evolutionary conserved nature of IFN-γ function in lower vertebrates including classical activation of phagocytes.
ISSN:1050-4648
1095-9947
DOI:10.1016/j.fsi.2010.07.010