Resveratrol inhibited LPS induced transcription of immune genes and secretion of eicosanoids in Atlantic salmon (Salmo salar), comparing mono-, co- and a novel triple cell culture model of head kidney leukocytes, liver cells and visceral adipocyte tissue

The aim was to study the effect of resveratrol on the interplay of inflammatory signals using three different cell models; a metabolic organ (liver), an endocrine organ (visceral adipose tissue, VAT) and an immune organ (head kidney leukocytes, HKL) following lipopolysaccharide challenge (LPS). Atlantic salmon HKL, liver cells and VAT were isolated from the same fish (n = 5). Each cell type was cultured either as mono-cultures, as co-cultures between HKL-liver cells, liver cells-VAT and HKL-VAT. Triple-cultures included all three tissues. In all cultures of HKL, LPS induced transcription of IL-1 beta, cox2, tnf alpha, IL-12, ccatt beta and Ahr were significantly inhibited by resveratrol (100, 200 mu M). Likewise, in all cultures of liver cells, the LPS induced expression of IL-1 beta was inhibited by resveratrol (100 and 200 mu M). HKL, both mono-cultures and triple-cultures and VAT cocultured with liver cells, showed LPS induced cox2 transcription that was inhibited by resveratrol (100 and 200 mu M). In contrast, VAT cultured as triple cultures, resveratrol 200 mu M particularly, in the presence of LPS, seemed to increase the expression of IL-1 beta and ccatt beta. Resveratrol did not significantly affect lox5 expression in any culture. HKL and VAT are the main producers of PGE2 in response to inflammatory stimuli. VAT showed high endogenous production of eicosanoids, particularly LTB4 and LTB5. Resveratrol inhibited bot LPS induced and endogenous eicosanoid production. Possible targets of resveratrol, Sirt1 and pAMPK were affected differently in the different cells and tissue studied.