Sal B effects on human monocyte-derived dendritic cell maturation blocked by PPARγ siRNA
FRIDAY, Dec. 2 (HealthDay News) -- Salvianolic acid B (Sal B) -- a herb-derived, water-soluble antioxidant known to help prevent atherosclerosis -- effectively suppresses the maturation of human monocyte-derived dendritic cells (h-monDCs), according to a study published in the December issue of the British Journal of Pharmacology.
Aijun Sun, M.D., Ph.D., from Fudan University in Shanghai, China, and colleagues investigated whether the anti-atherosclerotic effect of Sal B is mediated by suppressing h-monDC maturation. Purified human monocytes were incubated with granulocyte macrophage-colony stimulating factor and interleukin (IL)-4 to derive h-monDCs. The h-monDCs were stimulated by oxidized low-density lipoprotein (ox-LDL) in the presence or absence of peroxisome proliferator-activated receptor-γ (PPARγ) small interfering RNA (siRNA), after being pre-incubated with or without Sal B. Fluorescence-activated cell sorting was used to analyze the expression of h-monDC membrane molecules (CD40, CD86, CD1a, HLA-DR), an enzyme linked immunosorbent assay measured the cytokines, and Western blotting was used to determine the Toll-like receptor (TLR) 4-associated signalling pathway.
The investigators found that ox-LDL had multiple effects, including promotion of h-monDC maturation; stimulation of CD40, CD86, CD1a, and HLA-DR expression; production of IL-12, IL-10, and tumor necrosis factor-alpha; and up-regulation of TLR4 signalling. Sal B inhibited these effects. PPARγ activation, promotion of PPARγ nuclear translocation, attenuation of ox-LDL-induced up-regulation of TLR4 and myeloid differentiation primary-response protein 88, and inhibition of the downstream p38-mitogen activated protein kinase signalling cascade were also mediated by Sal B. These effects of Sal B were blocked by knocking down PPARγ with the corresponding siRNA.
"The possible anti-atherosclerotic effects of Sal B might be mediated by suppressing maturation of h-monDC," the authors write.
Abstract
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