Abstract
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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Hansson GK. Regulation of immune mechanisms in atherosclerosis. Ann NY Acad Sci 2001;947:157–165.
Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ. Immunobiology of dendritic cells. Annu Rev Immunol 2000;18:767–811.
Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998;392:245–252.
Millonig G, Niederegger H, Rabl W, Hochleitner BW, Hoefer D, Romani N, et al. Network of vascular associated dendritic cells in intima of healthy young individuals. Arterioscler Thromb Vasc Biol 2001;21:503–508.
Bobryshev YV, Lord RS. S-100 positive cells in human arterial intima and in atherosclerotic lesions. Cardiovasc Res 1995;29:689–696.
Bobryshev YV. Dendritic cells in atherosclerosis: current status of the problem and clinical relevance. Eur Heart J 2005;26:1700–1704.
Sun DD, Wang HC, Wang XB, Luo Y, Jin ZX, Li ZC, et al. Tanshinone IIA: a new activator of human cardiac KCNQ1/KCNE1(IKs) potassium channels. European Pharm 2008;590:317–321.
Zhou L, Zuo Z, Chow MS. Danshen: an overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. J Clin Pharm 2005;45:1345–1359.
Tu EY, Zhou YG, Wang ZH, Liang QS, Yang GT. Effects of tanshinone IIA on the myocardial hypertrophy signal transduction system protein kinase B in rats. Chin J Integr Med 2009;15:365–370.
Feng J, Zheng Z. Effect of sodium tanshinone II A sulfonate on cardiac myocyte hypertrophy and its underlying mechanism. Chin J Integr Med 2008;14:197–201.
Li SS, Feng J, Zheng Z, Liang QS. Effect of sodium tanshinone II A sulfonate on phosphorylation of extracellular signal-regulated kinase1/2 in angiotensin II-induced hypertrophy of myocardial cells. Chin J Integr Med 2008;14:123–127.
Fang ZY, Lin R, Yuan BX, Yang GD, Liu Y, Zhang H. Tanshinone IIA downregulates the CD40 expression and decreases MMP-2 activity on atherosclerosis induced by high fatty diet in rabbit. J Ethnopharmacol 2008;115:217–222.
Van Vré EA, Bult H, Hoymans VY, Van Tendeloo VF, Vrints CJ, Bosmans JM. Human C-reactive protein activates monocyte-derived dendritic cells and induces dendritic cellmediated T-cell activation. Arterioscler Thromb Vasc Biol 2008;28:511–518.
Iruretagoyena MI. The dendritic cell-T cell synapse as a determinant of autoimmune pathogenesis. Curr Pharm Des 2006;12:131–147.
Carreno BM, Collins M. The B7 family of ligands and its receptors: new pathways for costimulation and inhibition of immune responses. Annu Rev Immunol 2002;20:29–53.
Steinman RM, Hawiger D, Liu K, Bonifaz L, Bonnyay D, Mahnke K, et al. Dendritic cell function in vivo during the steady state: a role in peripheral tolerance. Ann NY Acad Sci 2003;987:15–25.
Bobryshev YV, Lord RS. Mapping of vascular dendritic cells in atherosclerotic arteries suggests their involvement in local immuneinflammatory reactions. Cardiovasc Res 1998;37:799–810.
Shoenfeld Y, Harats D, George J. Heat shock protein 60/65, beta 2-glycoprotein I and oxidized LDL as players in murine atherosclerosis. J Autoimmun 2000;15:199–202.
Aicher A, Heeschen C, Mohaupt M, Cooke JP, Zeiher AM, Dimmeler S. Nicotine strongly activates dendritic cell mediated adaptive immunity: potential role for progression of atherosclerotic lesions. Circulation 2003;107:604–611.
Yao K, Ge JB, Sun AJ, Hong XW, Shi HY, Huang RC, et al. Effects and mechanism of hyperglycemia on development and maturation and immune function of human monocyte derived dendritic cells. Chin J Cardiol (Chin) 2006;34:60–64.
Luo YK, Liang C, Xu CF, Jia Q, Huang D, Chen L, et al. Ciglitazone inhibits oxidized-low density lipoprotein induced immune maturation of dendritic cells. J Cardiovasc Pharmacol 2004;44:381–385.
Liang C, Jia Q, Luo Y, Huang D, Sun AJ, Xu CF. Pravastatin inhibits oxidized low density lipoprotein induced immune maturation of dendritic cells by upregulating PPARgamma: a new immunomodulatory mechanism of statins. Am J Cardiol 2004;94:103–107.
Ren ZH, Tong YH, Xu W, Ma J, Chen Y. TanshinoneII A attenuates infl ammatory responses of rats with myocardial infarction by reducing MCP-1 expression. Phytomedicine 2010;17:212–218.
Jang SI, Kim HJ, Kim YJ, Jeong SI, You YO. Tanshinone IIA inhibits LPS-induced NF-kappaB activation in RAW 264. 7 cells: possible involvement of the NIK-IKK, ERK1/2, p38 and JNK pathways. Eur J Pharmacol 2006;542:1–7.
Zhang Y, Wei L, Sun D, Cao F, Gao H, Zhao L, et al. Tanshinone IIA pretreatment protects myocardium against ischaemia/reperfusion injury through the phosphatidylinositol 3-kinase/Aktdependent pathway in diabetic rats. Diabetes Obes Metab 2010;12:316–322.
Mosaddik MA. In vitro cytotoxicity of tanshinones isolated from Salvia miltiorrhiza Bunge against P388 lymphocytic leukemia cells. Phytomedicine 2003;10:682–685.
Yuan SL, Wei YQ, Wang XJ, Xiao F, Li SF, Zhang J. Growth inhibition and apoptosis induction of tanshinone II-A on human hepatocellular carcinoma cells. World J Gastroenterol 2004;10:2024–2028.
Yang JF. Exploration method fordetection of tanshinoneIIA serum level by HPLC chromatograms. J Chongqing Med Univ (Chin) 2006;31:398–400.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by Administration of Traditional Chinese Medicine of Guangdong Province, China (No. 2010424)
Rights and permissions
About this article
Cite this article
Li, Hz., Lu, Yh., Huang, Gs. et al. Tanshinone II A inhibits dendritic cell-mediated adaptive immunity: Potential role in anti-atherosclerotic activity. Chin. J. Integr. Med. 20, 764–769 (2014). https://doi.org/10.1007/s11655-012-1213-9
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11655-012-1213-9