Solomonsterol A, a marine pregnane-X-receptor agonist, attenuates inflammation and immune dysfunction in a mouse model of arthritis

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

doi:10.3390/md12010036

Solomonsterol A, a marine pregnane-X-receptor agonist, attenuates inflammation and immune dysfunction in a mouse model of arthritis

Mar Drugs. 2013 Dec 24;12(1):36-53. doi: 10.3390/md12010036.

Authors

Andrea Mencarelli, Claudio D'Amore¹, Barbara Renga, Sabrina Cipriani, Adriana Carino, Valentina Sepe, Elisa Perissutti, Maria Valeria D'Auria, Angela Zampella², Eleonora Distrutti, Stefano Fiorucci

Affiliations

¹ Department of Experimental and Clinical Medicine, University of Perugia, Gambuli Street, S. Andrea delle Fratte, Perugia 06132, Italy. claudiodamore1983@gmail.com.
² Department of Experimental and Clinical Medicine, University of Perugia, Gambuli Street, S. Andrea delle Fratte, Perugia 06132, Italy. angela.zampella@unina.it.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents*
Arthritis, Rheumatoid / chemically induced
Arthritis, Rheumatoid / drug therapy*
Arthritis, Rheumatoid / pathology
C-Reactive Protein / metabolism
Cartilage / pathology
Chemokine CCL3 / metabolism
Chemokine CCL5 / metabolism
Cholanes / pharmacology*
Collagen Type II
Cytokines / blood
Hepatocytes / drug effects
Humans
Immunologic Deficiency Syndromes / drug therapy*
Interferon-gamma / metabolism
Interleukin-17 / metabolism
Liver / drug effects
Liver / metabolism
Lymph Nodes / drug effects
Lymph Nodes / metabolism
Mice, Inbred C57BL
Mice, Transgenic
Models, Molecular
Molecular Conformation
Porifera / chemistry*
Pregnane X Receptor
Receptors, Steroid / agonists*
Receptors, Steroid / biosynthesis
Receptors, Steroid / genetics
Sulfuric Acid Esters / pharmacology*
Transcriptional Activation
Tumor Necrosis Factor-alpha / metabolism

Substances

Anti-Inflammatory Agents
Chemokine CCL3
Chemokine CCL5
Cholanes
Collagen Type II
Cytokines
Interleukin-17
Pregnane X Receptor
Receptors, Steroid
Sulfuric Acid Esters
Tumor Necrosis Factor-alpha
cholan-2,3,24-tryl-2,3,24-trisulfate
Interferon-gamma
C-Reactive Protein