title: [Trichostatin A inhibits the activation of CD(4)(+) T cells by suppressing CD(28) expression in mice].
abstract: OBJECTIVE
  To investigate the mechanism of trichostatin A(TSA), a histone deacetylase (HDAC) inhibitor, in inhibiting the activation of CD(4)(+) T cells in mice.
  
  
  METHODS
  The CD(4)(+) T cells isolated from the spleen of C57BL mice were treated with different concentrations of TSA (2, 20, and 200 nmol/L) for 24 h, and CD(3), CD(28) and interleukin-2 (IL-2) mRNA levels were measured with reverse transcription-polymerase chain reaction. The protein expressions of CD(3), CD(28) and IL-2 were measured by fluorescence-activated cell sorting and ELISA analysis. ZAP70 and PI3K protein expression in CD(4)(+) T cells activated by CD(3) and CD(28) monoclonal antibody were analyzed by Western blotting.
  
  
  RESULTS
  TSA dose-dependently inhibited the transcription and protein expression of CD28 in CD(4)(+) T cells and reduced the expression of PI3K protein in activated CD(4)(+) T cells, without showing significant effect on the expression of ZAP70. TSA treatment of the cells also resulted in significantly decreased mRNA and protein expressions of IL-2 (P<0.01).
  
  
  CONCLUSIONS
  TSA can regulate the immunological activity of CD(4)(+) T cells by inducing mRNA and protein expressions of CD(28), which inhibits the activation of the co-stimulatory signal transduction in CD(4)(+) T cells and decreases the secretion of IL-2.
authors.affiliation: Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. weiqiang0915@163.com
authors.forename: Qiang
authors.initials: Q
authors.lastname: WEI
authors.forename: Xiao-yun
authors.initials: XY
authors.lastname: WEN
authors.forename: Chuan-fu
authors.initials: CF
authors.lastname: DU
authors.forename: Shao-yu
authors.initials: SY
authors.lastname: WU
authors.forename: Jun-sheng
authors.initials: JS
authors.lastname: YE
authors.forename: Zhong-hai
authors.initials: ZH
authors.lastname: LI
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007376:Interleukin-2; C012589:trichostatin A; D051997:ADP-ribosyl Cyclase 1