Salvianolic acid B suppresses maturation of human monocyte-derived dendritic cells by activating PPAR?.

ABSTRACT:

Background and purpose

Salvianolic acid B (Sal B), a water-soluble antioxidant derived from a Chinese 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 maturation of human monocyte-derived dendritic cells (h-monDC).

Experimental approach

h-monDC were derived by incubating purified human monocytes with GM-CSF and IL-4. h-monDC were pre-incubated with or without Sal B and stimulated by oxidized low-density lipoprotein (ox-LDL) in the presence or absence of PPAR? siRNA. Expression of h-monDC membrane molecules (CD40, CD86, CD1a, HLA-DR) were analysed by FACS, cytokines were measured by elisa and the TLR4-associated signalling pathway was determined by Western blotting.

Key results

Ox-LDL promoted h-monDC maturation, stimulated CD40, CD86, CD1a, HLA-DR expression and IL-12, IL-10, TNF-? production; and up-regulated TLR4 signalling. These effects were inhibited by Sal B. Sal B also triggered PPAR? activation and promoted PPAR? nuclear translocation, attenuated ox-LDL-induced up-regulation of TLR4 and myeloid differentiation primary-response protein 88 and inhibited the downstream p38-MAPK signalling cascade. Knocking down PPAR? with the corresponding siRNA blocked these effects of Sal B.

Conclusions and implications

Our data suggested that Sal B effectively suppressed maturation of h-monDC induced by ox-LDL through PPAR? activation.

SUBMITTER: Sun A 

PROVIDER: S-EPMC3246666 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature