Trichostatin A inhibits the activation of CD(4)(+) T cells by suppressing CD(28) expression in mice.
- Author:
Qiang WEI
1
;
Xiao-yun WEN
;
Chuan-fu DU
;
Shao-yu WU
;
Jun-sheng YE
;
Zhong-hai LI
Author Information
- Publication Type:Journal Article
- MeSH: ADP-ribosyl Cyclase 1; antagonists & inhibitors; Animals; CD4-Positive T-Lymphocytes; drug effects; metabolism; Cell Line; Female; Histone Deacetylase Inhibitors; pharmacology; Hydroxamic Acids; pharmacology; Interleukin-2; metabolism; Lymphocyte Activation; drug effects; Mice; Mice, Inbred C57BL; Signal Transduction; drug effects
- From: Journal of Southern Medical University 2011;31(3):423-428
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the mechanism of trichostatin A(TSA), a histone deacetylase (HDAC) inhibitor, in inhibiting the activation of CD(4)(+) T cells in mice.
METHODSThe 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.
RESULTSTSA 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).
CONCLUSIONTSA 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.
