Sinomenine inhibits maturation of monocyte-derived dendritic cells through blocking activation of NF-kappa B.

Abstract

Sinomenine, a purified alkaloid extracted from Sinomenium acutum, has been employed to treat arthritis for a long time. Previous studies have shown that sinomenine has favorable function of immunosuppression, but the exact mechanism has not been illustrated yet. In this study, we investigated the effect of sinomenine on human monocyte-derived dendritic cells (DCs). Lipopolysaccharide (LPS) induced DCs, exposed to sinomenine or only medium, were tested for their maturation parameters, cytokine expression, mixed lymphocyte reaction, activity and translocation of nuclear factor-kappa B (NF-kappaB) and phosphorylation of p38 stress-activated protein kinase (p38SAPK). Down-regulated membrane expression of CD40, CD80, CD83, CD86, and HLA-DR were found on DCs exposed to sinomenine. Similar result was noticed in their IL-12 production. Reduced activity and translocation of NF-kappaB was also detected in sinomenine treated DCs, except for the level of p38SAPK phosphorylation. Our results support the conclusion that sinomenine inhibits immune responses through suppressing the functions of antigen-presenting cells and NF-kappaB pathway is involved in their maturation cascade and T-cell activation. The findings indicate the potency for sinomenine to be generally used in DCs-mediated autoimmune diseases.

• Authors: Yi Zhao, Juan Li, Keqiang Yu, Yi Liu, Xiaoguang Chen
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 7 Issue 5 Pg. 637-45 (May 2007) ISSN: 1567-5769 [Print] Netherlands
• PMID: 17386411 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cytokines
• Indicators and Reagents
• Morphinans
• NF-kappa B
• Interleukin-12
• sinomenine
• p38 Mitogen-Activated Protein Kinases

Topics

• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Blotting, Western
• Cytokines (biosynthesis)
• Dendritic Cells (drug effects)
• Electrophoretic Mobility Shift Assay
• Enzyme Activation (drug effects)
• Flow Cytometry
• Fluorescent Antibody Technique
• Humans
• Indicators and Reagents
• Interleukin-12 (biosynthesis)
• Lymphocyte Culture Test, Mixed
• Monocytes (drug effects)
• Morphinans (pharmacology)
• NF-kappa B (antagonists & inhibitors)
• Phenotype
• Reverse Transcriptase Polymerase Chain Reaction
• Stimulation, Chemical
• Translocation, Genetic (drug effects)
• p38 Mitogen-Activated Protein Kinases (biosynthesis)