4-Methylenesterols from Theonella swinhoei sponge are natural pregnane-X-receptor agonists and farnesoid-X-receptor antagonists that modulate innate immunity De Marino, S. Ummarino, R. D'Auria, M. V. Chini, M. G. Bifulco, G. D'Amore, C. Renga, B. Mencarelli, A. /Petek, Sylvain Fiorucci, S. Zampella, A. Marine sponge Theonella swinhoei Nuclear receptors Farnesoid-X-receptor Pregnane-X-receptor 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. 2012 text https://www.documentation.ird.fr/hor/fdi:010055824 fdi:010055824 De Marino S., Ummarino R., D'Auria M. V., Chini M. G., Bifulco G., D'Amore C., Renga B., Mencarelli A., Petek Sylvain, Fiorucci S., Zampella A.. 4-Methylenesterols from Theonella swinhoei sponge are natural pregnane-X-receptor agonists and farnesoid-X-receptor antagonists that modulate innate immunity. 2012, 77 (5), 484-495 EN