title: Solomonsterol A, a marine pregnane-X-receptor agonist, attenuates inflammation and immune dysfunction in a mouse model of arthritis.
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.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mencarelli
authors.affiliation: Department of Experimental and Clinical Medicine, University of Perugia, Gambuli Street, S. Andrea delle Fratte, Perugia 06132, Italy. claudiodamore1983@gmail.com.
authors.forename: Claudio
authors.initials: C
authors.lastname: D'Amore
authors.forename: Barbara
authors.initials: B
authors.lastname: Renga
authors.forename: Sabrina
authors.initials: S
authors.lastname: Cipriani
authors.forename: Adriana
authors.initials: A
authors.lastname: Carino
authors.forename: Valentina
authors.initials: V
authors.lastname: Sepe
authors.forename: Elisa
authors.initials: E
authors.lastname: Perissutti
authors.forename: Maria Valeria
authors.initials: MV
authors.lastname: D'Auria
authors.affiliation: Department of Experimental and Clinical Medicine, University of Perugia, Gambuli Street, S. Andrea delle Fratte, Perugia 06132, Italy. angela.zampella@unina.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Zampella
authors.forename: Eleonora
authors.initials: E
authors.lastname: Distrutti
authors.forename: Stefano
authors.initials: S
authors.lastname: Fiorucci
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D002356:Cartilage / Q000473:pathology; D054405:Chemokine CCL3 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D002757:Cholanes / Q000494:pharmacology*; D024043:Collagen Type II; D016207:Cytokines / Q000097:blood; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy*; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008958:Models, Molecular; D008968:Molecular Conformation; D011161:Porifera / Q000737:chemistry*; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000819:agonists* / Q000096:biosynthesis / Q000235:genetics; D013463:Sulfuric Acid Esters / Q000494:pharmacology*; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D054405:Chemokine CCL3; D018946:Chemokine CCL5; D002757:Cholanes; D024043:Collagen Type II; D016207:Cytokines; D020381:Interleukin-17; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D013463:Sulfuric Acid Esters; D014409:Tumor Necrosis Factor-alpha; C561233:cholan-2,3,24-tryl-2,3,24-trisulfate; D007371:Interferon-gamma; D002097:C-Reactive Protein