Solomonsterol A, a Marine Pregnane-X-Receptor Agonist, Attenuates Inflammation and Immune Dysfunction in a Mouse Model of Arthritis

被引：21

作者：

Mencarelli, Andrea ^{[1
]}

D'Amore, Claudio ^{[1
]}

Renga, Barbara ^{[1
]}

Cipriani, Sabrina ^{[1
]}

Carino, Adriana ^{[1
]}

Sepe, Valentina ^{[2
]}

Perissutti, Elisa ^{[2
]}

D'Auria, Maria Valeria ^{[2
]}

Zampella, Angela ^{[2
]}

Distrutti, Eleonora ^{[3
]}

Fiorucci, Stefano ^{[1
]}

机构：

[1] Univ Perugia, Dept Expt & Clin Med, I-06132 Perugia, Italy

[2] Univ Naples Federico II, Dept Pharm, I-80131 Naples, Italy

[3] Univ & City Hosp Perugia, I-06100 Perugia, Italy

来源：

MARINE DRUGS | 2014年 / 12卷 / 01期

关键词：

marine sponge; Theonella swinhoei; rheumatoid arthritis; inflammation; pregnane X receptor (PXR); solomonsterol A; NF-KAPPA-B; INTESTINAL EPITHELIAL-CELLS; RHEUMATOID-ARTHRITIS; THEONELLA-SWINHOEI; NUCLEAR RECEPTORS; COLLAGEN ANTIBODY; GENE-EXPRESSION; INNATE IMMUNITY; BOWEL-DISEASE; PXR;

D O I：

10.3390/md12010036

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In the present study we provide evidence that solomonsterol A, a selective pregnane X receptor (PXR) agonist isolated from the marine sponge Theonella swinhoei, exerts anti-inflammatory activity and attenuates systemic inflammation and immune dysfunction in a mouse model of rheumatoid arthritis. Solomonsterol A was effective in protecting against the development of arthritis induced by injecting transgenic mice harboring a humanized PXR, with anti-collagen antibodies (CAIA) with beneficial effects on joint histopathology and local inflammatory response reducing the expression of inflammatory markers (TNF alpha, IFN gamma and IL-17 and chemokines MIP1 alpha and RANTES) in draining lymph nodes. Solomonsterol A rescued mice from systemic inflammation were assessed by measuring arthritis score, CRP and cytokines in the blood. In summary, the present study provides a molecular basis for the regulation of systemic local and systemic immunity by PXR agonists.

引用

页码：36 / 53

页数：18

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