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. (2012). 4-Methylenesterols from Theonella swinhoei sponge are natural pregnane-X-receptor agonists and farnesoid-X-receptor antagonists that modulate innate immunity. Steroids, 77 (5), p. 484-495. ISSN 0039-128X.
Titre du document
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.
Source
Steroids, 2012,
77 (5), p. 484-495 ISSN 0039-128X
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.
