Impact of cyclosporine A on the expression of T-bet, GATA-3, relevant signal transduction molecules, cytokine and Th1/Th2 balance in patients with chronic aplastic anemia.
- Author:
Jun LI
1
;
Yong-Ming ZHOU
;
Ming-Hui HU
;
Wei-Ling SUN
;
Zhi-Zhong XUE
Author Information
1. Department of Hematology, Jiangsu Provincial Hospital of Chinese Traditional Medicine, Nanjing University of Chinese Traditional Medicine, Nanjing 210029, Jiangsu Province, China.
- Publication Type:Journal Article
- MeSH:
Adolescent;
Adult;
Aged;
Anemia, Aplastic;
drug therapy;
immunology;
metabolism;
Case-Control Studies;
Cyclosporine;
pharmacology;
Female;
GATA3 Transcription Factor;
metabolism;
Humans;
Interferon-gamma;
metabolism;
Interleukin-12;
metabolism;
Interleukin-4;
metabolism;
Male;
Middle Aged;
STAT4 Transcription Factor;
metabolism;
STAT6 Transcription Factor;
metabolism;
Signal Transduction;
T-Box Domain Proteins;
metabolism;
Th1 Cells;
drug effects;
Th2 Cells;
drug effects;
Young Adult
- From:
Journal of Experimental Hematology
2010;18(5):1211-1219
- CountryChina
- Language:Chinese
-
Abstract:
The study was aimed to explore the effects of T-bet (T-box expressed in T cell), GATA-3(GATA binding protein 3) and relevant signal transduction pathways on the immune-related pathogenesis of chronic aplastic anemia (CAA), and to investigate the immunological regulation mechanism in the treatment of CAA by using cyclosporine A (CsA) at the level of Th cell imbalance, transcriptional factors, and relevant signal pathways. The real-time fluorescent quantitative polymerase chain reaction (real-time FQ-PCR) was used to determine the mRNA expression of T-bet, GATA-3, signal transducers and activators of transcription 4 (STAT4) and signal transducers and activators of transcription 6 (STAT6) in peripheral blood mononuclear cell (PBMNC) of CAA patients before and after treatment with CsA; the flow cytometry (FCM) and enzyme linked immunosorbent assay (ELISA) were used to determine the Th1/Th2 proportion in peripheral blood, and levels of IFN-γ, IL-12 and IL-4 in PBMNC-cultured supernatant. Healthy people were included to test the above indexes. The results showed that the mRNA expression of PBMNC T-bet, STAT4, T-bet/GATA-3 ratio, Th1 proportion, Th1/Th2 ratio and levels of IFN-γ and IL-12 in PBMNC-cultured supernatant of CAA patients were significantly higher than those of healthy people (p < 0.01). After treating with CsA for 6 months of CsA treatment, expression of T-bet, STAT4, T-bet/GATA-3 ratio, Th1 proportion, IFN-γ and IL-12 levels were lower than before, however, the expression of T-bet, STAT4, T-bet/GATA-3 ratio, Th1 proportion and IFN-γ had not been reduced to normal state. Compared to healthy people, no significant difference existed in the mRNA expression of GATA-3, STAT6, Th2 proportion, as well as level of IL-4 before and after treatment (p>0.05). It is concluded that the abnormal activation of IFN-γ/T-bet and IL-12/STAT4 pathways, as well as Th balance deviating to Th1 excursion play vital roles in the immunological pathogenesis of AA. CsA lowers the abnormal activation of IFN-γ/T-bet and IL-12/STAT4 pathways to correct Th1 hyperpolarization, which may reduce the abnormally activated cell-mediated immunity and relax hematopoietic depression of AA patients.
