Molecular Cloning, Tissue Distribution, and Pharmacological Characterization of GPR84 in Grass Carp (Ctenopharyngodon Idella).

Simple Summary: GPR84 is a G protein-coupled receptor expressed in immune cells. In mammals and amphibians, it is activated by medium-chain fatty acids and plays critical roles in inflammation and eye development. However, our understanding of GPR84 in fish remains limited. In this study, we successfully cloned the coding sequence of grass carp GPR84, revealing its high expression in the liver and spleen. In cells transfected with ciGPR84, we observed its responsiveness to medium-chain fatty acids such as capric acid, undecanoic acid, and lauric acid. Surprisingly, ciGPR84 did not respond to a synthetic activator called diindolylmethane. Notably, we found that lauric acid and capric acid exhibited the strongest activation and inhibition of ERK and cAMP signaling, respectively, suggesting their potential as immune modulators. These findings provide valuable insights for mitigating chronic inflammation in farmed fish, especially grass carp. The G-protein-coupled receptor GPR84, activated by medium-chain fatty acids, primarily expressed in macrophages and microglia, is involved in inflammatory responses and retinal development in mammals and amphibians. However, our understanding of its structure, function, tissue expression, and signaling pathways in fish is limited. In this study, we cloned and characterized the coding sequence of GPR84 (ciGPR84) in grass carp. A phylogenetic analysis revealed its close relationship with bony fishes. High expression levels of GPR84 were observed in the liver and spleen. The transfection of HEK293T cells with ciGPR84 demonstrated its responsiveness to medium-chain fatty acids and diindolylmethane (DIM). Capric acid, undecanoic acid, and lauric acid activated ERK and inhibited cAMP signaling. Lauric acid showed the highest efficiency in activating the ERK pathway, while capric acid was the most effective in inhibiting cAMP signaling. Notably, DIM did not activate GPR84 in grass carp, unlike in mammals. These findings provide valuable insights for mitigating chronic inflammation in grass carp farming and warrant further exploration of the role of medium-chain fatty acids in inflammation regulation in this species. [ABSTRACT FROM AUTHOR]