%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A De Marino, S.
%A Ummarino, R.
%A D'Auria, M. V.
%A Chini, M. G.
%A Bifulco, G.
%A D'Amore, C.
%A Renga, B.
%A Mencarelli, A.
%A Petek, Sylvain
%A Fiorucci, S.
%A Zampella, A.
%T 4-Methylenesterols from Theonella swinhoei sponge are natural pregnane-X-receptor agonists and farnesoid-X-receptor antagonists that modulate innate immunity
%D 2012
%L fdi:010055824
%G ENG
%J Steroids
%@ 0039-128X
%K Marine sponge ; Theonella swinhoei ; Nuclear receptors ; Farnesoid-X-receptor ; Pregnane-X-receptor
%M ISI:000303084000019
%N 5
%P 484-495
%R 10.1016/j.steroids.2012.01.006
%U https://www.documentation.ird.fr/hor/fdi:010055824
%> https://www.documentation.ird.fr/intranet/publi/2012/05/010055824.pdf
%V 77
%W Horizon (IRD)
%X 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