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-κB) 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-κB 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-κB 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.