Horizon 1 1 17 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES Steroids 484-495 Marine sponge Theonella swinhoei Nuclear receptors Farnesoid-X-receptor Pregnane-X-receptor 2012 fdi:010055824 ENG Steroids 0039-128X ISI:000303084000019 5 10.1016/j.steroids.2012.01.006 https://www.documentation.ird.fr/hor/fdi:010055824 https://www.documentation.ird.fr/intranet/publi/2012/05/010055824.pdf 77 Horizon (IRD) We report the isolation and the structural elucidation of a family of polyhydroxylated steroids from the marine sponge Theonella swinhoei. Decodification of interactions of these family with nuclear receptors shows that these steroids are potent agonists of human pregnane-X-receptor (PXR) and antagonists of human farnesoid-X-receptor (FXR) with the putative binding mode to nuclear receptors (NRs) obtained through docking experiments. By using monocytes isolated from transgenic mice harboring hPXR. we demonstrated that swinhosterol B counter-regulates induction of pro-inflammatory cytokines in a PXR-dependent manner. Exposure of CD4(+) T cells to swinhosterol B upregulates the expression of IL-10 causing a shift toward a T cells regulatory phenotype in a PXR dependent manner. These results pave the way to development of a dual PXR agonist/FXR antagonist with a robust immunomodulatory activity and endowed with the ability to modulate the expression of bile acid-regulated genes in the liver. 035 UR148