Functional analysis of carp interferon-gamma: evolutionary conservation of classical phagocyte activation.
In teleost fish two IFN-gamma 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-gamma function is associated with the IFN-gamma2 cluster. We investigated the evolutionary conservation of the IFN-gamma function, inducing classical activation of phagocytes, thus skewing towards a Th1-like profile of immune activation. Recombinant proteins for the carp IFN-gamma sequences of both clusters were made and we studied their effects on expression of proinflammatory mediators. Carp IFN-gamma2, in contrast to carp IFN-gamma1, 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-1beta, TNFalpha and the IL-12 subunits p35 and p40. In contrast, like in mammals, the CXCL8-like cytokines are LPS but not IFN-gamma sensitive. These results corroborate an evolutionary conserved nature of IFN-gamma function in lower vertebrates including classical activation of phagocytes.
Arts
J A J
JA
Cell Biology & Immunology Group, Wageningen University, Marijkeweg 40, P.O. Box 338, 6700 AH Wageningen, The Netherlands.
Tijhaar
E J
EJ
Chadzinska
M
M
Savelkoul
H F J
HF
Verburg-van Kemenade
B M L
BM
D000818:Animals; D005075:Biological Evolution; D002347:Carps / Q000235:genetics / Q000276:immunology*; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis / Q000502:physiology; D002846:Chromatography, Affinity; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010586:Phagocytes / Q000276:immunology*; D016897:Respiratory Burst; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018925:Chemokines; D016207:Cytokines; D017931:DNA Primers; D018076:DNA, Complementary; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II