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: 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
• Journal: Marine drugs (Mar Drugs) Vol. 12 Issue 1 Pg. 36-53 (Dec 24 2013) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 24368568 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• Animals
• Anti-Inflammatory Agents
• Arthritis, Rheumatoid (chemically induced, drug therapy, 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, metabolism)
• Lymph Nodes (drug effects, metabolism)
• Mice, Inbred C57BL
• Mice, Transgenic
• Models, Molecular
• Molecular Conformation
• Porifera (chemistry)
• Pregnane X Receptor
• Receptors, Steroid (agonists, biosynthesis, genetics)
• Sulfuric Acid Esters (pharmacology)
• Transcriptional Activation
• Tumor Necrosis Factor-alpha (metabolism)