title: Tanshinone II A inhibits dendritic cell-mediated adaptive immunity: potential role in anti-atherosclerotic activity.
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.
authors.affiliation: Integrative Hospital, College of Chinese Medicine, Southern Medical University, Guangzhou, 510315, China.
authors.forename: Hong-zhan
authors.initials: HZ
authors.lastname: Li
authors.forename: Yong-heng
authors.initials: YH
authors.lastname: Lu
authors.forename: Guang-sheng
authors.initials: GS
authors.lastname: Huang
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Zhi-liang
authors.initials: ZL
authors.lastname: Li
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000938:Antigen-Presenting Cells / Q000187:drug effects; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology; D051940:B7-2 Antigen / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects
chemical_list: D045784:Abietanes; D051940:B7-2 Antigen; D016207:Cytokines; D018836:Inflammation Mediators; C021751:tanshinone