G protein-coupled bile acid receptor 1 reduced hepatic immune response and inhibited NFκB, PI3K/AKT, and PKC/P38 MAPK signaling pathway in hybrid grouper
The mammalian G protein-coupled bile acidity receptor 1 (TGR5) is active in the inflammatory response. However, the functions of TGR5 within the immune response of fish remain unclear. Within this study, the entire-length sequence of tgr5 from hybrid grouper (Epinephelus fuscoguttatus ? × E. lanceolatus ?) was cloned, and also the purpose of TGR5 within the immune response was explored. The outcomes demonstrated the ORF of tgr5 gene in hybrid grouper was 1029 bp and encoded 342 proteins. Activation of TGR5 by INT-777 considerably decreased those activities and mRNA expression of TNFa and IL1ß, whereas inhibition of TGR5 by SBI-115 demonstrated the alternative effect. SBI-115 treatment considerably elevated the expression of phosphorylated inhibitor ?B a (p-IKBa) protein. Following the INT-777 treatment, the power of protein kinase C (PKC) and expression from the p38 mitogen-activated protein kinases (p38a), p38b and p38c, were considerably decreased in vivo. INT-777 agonist considerably decreased the expression of phosphorylated phosphoinositide 3-kinase (p-PI3K) protein and the number of phosphorylated and nonphosphorylated serine/threonine-protein kinase (p-AKT/AKT). To conclude, activation of hepatic TGR5 inhibited the PKC/P38 MAPK, PI3K/AKT, NF?B signaling path and improved hepatic immune responses of hybrid grouper in vivo as well as in vitro.