Growth differentiation factor 15, a novel acute phase response gene in Japanese flounder, Paralichthys olivaceus.

The acute phase response, an important aspect of innate immunity, leads to the production of acute phase proteins (APPs) in the liver which would consequently help restore homeostasis to the body. Here, we identified a novel cytokine, growth differentiation factor 15 (GDF15) from Japanese flounder. Three out of the 384 EST sequences derived from liver of Japanese flounder treated with formalin-killed Edwardsiella tarda showed significant homology with GDF of various species. After obtaining the full-length cDNA, the deduced amino acid sequence exhibited low identity (<30%) with GDF15s of higher vertebrates. The predicted ORF of JFGDF15 revealed a signaling peptide at the N terminal, a TGFbeta propeptide domain and a TGFbeta domain. The mature peptide domain of JFGDF15 contains an RXXR motif, a furin cleavage site, required for the release of the mature peptide and conserved amino acids, which are signature features of TGFbeta superfamily proteins. JFGDF15 mRNA transcripts were detected in fish, 6h post-injection with PBS. The transcripts were highly up-regulated in liver at 6h post-injection with formalin-killed E. tarda. Moreover, up-regulation of the transcripts was also observed at 12h post-injection with formalin-killed Streptococcus iniae.