De Marino S. auteur aut IRD Ummarino R. auteur aut IRD D'Auria M. V. auteur aut IRD Chini M. G. auteur aut IRD Bifulco G. auteur aut IRD D'Amore C. auteur aut IRD Renga B. auteur aut IRD Mencarelli A. auteur aut IRD Petek Sylvain auteur aut IRD Fiorucci S. auteur aut IRD Zampella A. auteur aut IRD text journalArticle eng text/pdf born digital access 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. specialized Marine sponge Theonella swinhoei Nuclear receptors Farnesoid-X-receptor Pregnane-X-receptor 035 77 5 484-495 2012 0039-128X https://www.documentation.ird.fr/hor/fdi:010055824 10.1016/j.steroids.2012.01.006 0039-128X [F B010055824] https://www.documentation.ird.fr/hor/fdi:010055824 https://www.documentation.ird.fr/intranet/publi/2012/05/010055824.pdf Accès réservé (Intranet de l'IRD) IRD - Base Horizon / Pleins textes 2012-06-01 2017-08-23 fdi:010055824 fre