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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 / 中国实验血液学杂志
Journal of Experimental Hematology ; (6): 1211-1219, 2010.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-332390
Responsible library: WPRO
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.
Subject(s)
Full text: Available Database: WPRIM (Western Pacific) Main subject: Pharmacology / Signal Transduction / Case-Control Studies / Interleukin-4 / Interferon-gamma / Cyclosporine / Th2 Cells / Th1 Cells / Interleukin-12 / T-Box Domain Proteins Type of study: Observational study Limits: Adolescent / Adult / Aged / Female / Humans / Male Language: Chinese Journal: Journal of Experimental Hematology Year: 2010 Document type: Article
Full text: Available Database: WPRIM (Western Pacific) Main subject: Pharmacology / Signal Transduction / Case-Control Studies / Interleukin-4 / Interferon-gamma / Cyclosporine / Th2 Cells / Th1 Cells / Interleukin-12 / T-Box Domain Proteins Type of study: Observational study Limits: Adolescent / Adult / Aged / Female / Humans / Male Language: Chinese Journal: Journal of Experimental Hematology Year: 2010 Document type: Article
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