Tanshinone II A inhibits dendritic cell-mediated adaptive immunity: Potential role in anti-atherosclerotic activity

• Published in: Chinese journal of integrative medicine Vol. 20; no. 10; pp. 764 - 769
• Main Authors: Li, Hong-zhan, Lu, Yong-heng, Huang, Guang-sheng, Chen, Qi, Fu, Qiang, Li, Zhi-liang
• Format: Journal Article
• Language: English
• Published: Heidelberg Chinese Association of Traditional and Western Medicine 01.10.2014
• Subjects: Antigen-Presenting Cells - drug effects; Atherosclerosis - immunology; Atherosclerosis - pathology; B7-2 Antigen - metabolism; Cell Membrane - drug effects; Cell Membrane - metabolism; Cytokines - secretion; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - secretion; Diterpenes, Abietane - pharmacology; Endocytosis - drug effects; Flow Cytometry; Humans; Immunity, Cellular - drug effects; Inflammation Mediators - metabolism; Lymphocyte Activation - drug effects; Medicine; Medicine & Public Health; Original Article; atherosclerosis; dendritic cells; immunity; tanshinone II A
• ISSN: 1672-0415; 1993-0402
• DOI: 10.1007/s11655-012-1213-9

Objective Antigen-presenting cells such as monocytes and dendritic cells (DCs) stimulate T-cell proliferation and activation during adaptive immunity. This cellular interaction plays a role in the growth of atherosclerotic plaques. Tanshinone II A (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 interleukin (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 II (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.