Abstract P304: Salvianolic Acid B Suppresses Human Monocyte-Derived Dendritic Cell Maturation via PPARγ Activation

Abstract

Background and purpose: Salvianolic acid B (Sal B), a water-soluble antioxidant derived from a medicinal herb, is known to be effective in the prevention of atherosclerosis. Here, we tested the hypothesis that the anti-atherosclerotic effect of Sal B might be mediated by suppressing human monocyte-derived dendritic cells (DCs) maturation. Experimental approach: DCs was derived by incubating purified human monocytes with GM-CSF and IL-4. DCs was pre-incubated with or without Sal B and stimulated by oxidized low density lipoprotein (ox-LDL) in the presence or absence of PPAR-γ siRNA. Expression of DCs membrane molecules were analyzed by FACS, cytokines were measured by ELISA, and TLR4 associated signaling pathway was determined by Western blotting. Key results: Ox-LDL promoted DCs maturation, stimulated CD40, CD86, CD1a, HLA-DR expression and IL-12, IL-10, TNF-α production and upregulated TLR4 signaling. These effects could be significantly inhibited by Sal B. Sal B also triggered PPAR-γ activation and promoted PPAR-γ nuclear translocation, attenuated ox-LDL-induced upregulation of TLR4 and myeloid differentiation primary-response protein 88 (MyD88), and inhibited downstream p38-MAPK signaling cascade. Knocking down PPAR-γ through siRNA transfection significantly blocked above mentioned effects of Sal B. Conclusions and implications: Our data suggested that Sal B effectively suppressed ox-LDL-induced DCs maturation through PPAR-γ activation.