期刊
STEROIDS
卷 77, 期 5, 页码 484-495出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.steroids.2012.01.006
关键词
Marine sponge; Theonella swinhoei; Nuclear receptors; Farnesoid-X-receptor; Pregnane-X-receptor
资金
- MIUR Sostanze ad attivita antitumorale: isolamento da fonti marine, sintesi di analoghi e ulteriore sviluppo della chemoteca LIBIO-MOL Rome, Italy
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. (C) 2012 Elsevier Inc. All rights reserved.
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