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

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.