Solomonsterol A,a Marine Pregnane-X-Receptor Agonist,Attenuates Inflammation and Immune Dysfunction in a Mouse Model of Arthritis |
| |
| Authors: | Andrea Mencarelli Claudio D’Amore Barbara Renga Sabrina Cipriani Adriana Carino Valentina Sepe Elisa Perissutti Maria Valeria D’Auria Angela Zampella Eleonora Distrutti Stefano Fiorucci |
| |
| Affiliation: | 1.Department of Experimental and Clinical Medicine, University of Perugia, Gambuli Street, S. Andrea delle Fratte, Perugia 06132, Italy; E-Mails: (A.M.); (B.R.); (S.C.); (A.C.); (S.F.);2.Department of Pharmacy, University of Naples “Federico II”, D. Montesano Street, 49, Naples 80131, Italy; E-Mails: (V.S.); (E.P.); (M.V.D.A.);3.University and City Hospital of Perugia, Perugia 06100, Italy; E-Mail: |
| |
| Abstract: | 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 (TNFα, IFNγ and IL-17 and chemokines MIP1α 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. |
| |
| Keywords: | marine sponge Theonella swinhoei rheumatoid arthritis inflammation pregnane X receptor (PXR) solomonsterol A |
|
|
