Identification and characterization of the prepro-vasoactive intestinal peptide gene from the teleost Paralichthys olivaceus

The gene encoding the prepro form of a vasoactive intestinal peptide (VIP) was cloned, and its structural organization and expression profiles were determined in the teleost Paralichthys olivaceus. The prepro-VIP encodes both a VIP and a peptide-histidine-isoleucine (PHI). The VIP gene comprises six exons with two distinct peptides encoded on separate exons, i.e., PHI on exon III and VIP on exon IV. Several elements involved in cytokine-mediated activation are highly conserved in an 806-bp segment of the 5′-flanking region: cAMP responsive elements (CREs), binding sites for nuclear factor IL-6 (NF-IL-6), activating protein-1 (AP-1), stimulating protein-1 (Sp-1), two IL-6 responsive element binding proteins (IL-6 RE-BPs), and signal transducers and activators of transcription (STAT). The mRNA transcripts in normally conditioned fish are expressed in the brain, intestine, stomach, pyloric ceca, spleen, and heart, but not in the muscle, liver, head or trunk kidneys, and gill. However, prepro-VIP mRNA expression in the spleen and head kidney is significantly up- and down-regulated when exposed to an artificial bacterial challenge by Edwardsiella tarda. These results suggest that the typical features of neuropeptide VIPs are evolutionarily conserved from non-mammalian vertebrates to mammals and that the flounder VIP plays an important role in the immune system, especially inflammatory processes.