601. Solomonsterol A, a marine pregnane-X-receptor agonist, attenuates inflammation and immune dysfunction in a mouse model of arthritis.
- Author
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Mencarelli A, D'Amore C, Renga B, Cipriani S, Carino A, Sepe V, Perissutti E, D'Auria MV, Zampella A, Distrutti E, and Fiorucci S
- Subjects
- Animals, Arthritis, Rheumatoid chemically induced, Arthritis, Rheumatoid pathology, C-Reactive Protein metabolism, Cartilage pathology, Chemokine CCL3 metabolism, Chemokine CCL5 metabolism, Collagen Type II, Cytokines blood, Hepatocytes drug effects, Humans, 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, Pregnane X Receptor, Receptors, Steroid biosynthesis, Receptors, Steroid genetics, Transcriptional Activation, Tumor Necrosis Factor-alpha metabolism, Anti-Inflammatory Agents, Arthritis, Rheumatoid drug therapy, Cholanes pharmacology, Immunologic Deficiency Syndromes drug therapy, Porifera chemistry, Receptors, Steroid agonists, Sulfuric Acid Esters pharmacology
- 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.
- Published
- 2013
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