Tanshinone ⅡA Inhibits Dendritic Cell-mediated Adaptive Immunity：Potential Role in Anti-atherosclerotic Activity

• Published in: 中国结合医学杂志：英文版 2014 (10), p.764-769
• Main Author: 黎洪展 吕永恒 黄光胜 陈琪 付强 李志樑
• Format: Article
• Language: English
• Subjects: 丹参酮; 动脉粥样硬化; 巨噬细胞集落刺激因子; 树突状细胞; 潜在作用; 炎性细胞因子; 获得性免疫; 酶联免疫吸附测定法
• ISSN: 1672-0415; 1993-0402

Objective：Antigen-presenting cells such as monocytes and dendritic cells（DCs） stimulate T-ceil proliferation and activation during adaptive immunity.This cellular interaction plays a role in the growth of atherosclerotic plaques.Tanshinone ⅡA（TSN） had been shown to decrease the growth of atherosclerotic lesions.We therefore investigated the ability of TSN to inhibit human monocyte-derived DCs and their T-cellstimulatory capacity.Methods：DCs derived from human monocytes cultured with recombinant human interieukin（IL）-4 and recombinant human granulocyte-macrophage colony-stimulating factor were co-cultured with TSN and lipopolysaccharide for 48 h.Phosphate-buffered saline was used as a negative control.Activation markers and the capacity of DCs for endocytosis were measured by flow cytometry,and proinflammatory cytokines were measured by enzyme-linked immunosorbent assays.DCs were co-cultured with lymphocytes to measure T-cell proliferation and IL-2 secretion by mixed lymphocyte reactions.Results：TSN dose-dependently attenuated DC expression of costimulatory molecules（CD86）,and decreased expression of major histocompatibility complex class I（human loukocyte antigen-DR） and adhesion molecules（CD54）.Moreover,TSN reduced secretion of the proinflammatory cytokines IL-12 and IL-1 by human DCs,and restored the capacity for endocytosis.Finally,TSN-preincubated DCs showed a reduced capacity to stimulate T-cell proliferation and cytokine secretion.Conclusions：TSN inhibits DC maturation and decreases the expression of proinflammatory cytokines,while impairing their capacity to stimulate T-cell proliferation and cytokine secretion.These effects may contribute to the influence of TSN on the progression of atherosclerotic lesions.