PMID- 21129263 OWN - NLM STAT- MEDLINE DCOM- 20111013 LR - 20161018 IS - 1009-2137 (Print) IS - 1009-2137 (Linking) VI - 18 IP - 5 DP - 2010 Oct TI - [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]. PG - 1211-9 AB - 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-gamma, 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-gamma 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-gamma and IL-12 levels were lower than before, however, the expression of T-bet, STAT4, T-bet/GATA-3 ratio, Th1 proportion and IFN-gamma 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-gamma/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-gamma/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. FAU - Li, Jun AU - Li J AD - Department of Hematology, Jiangsu Provincial Hospital of Chinese Traditional Medicine, Nanjing University of Chinese Traditional Medicine, Nanjing 210029, Jiangsu Province, China. FAU - Zhou, Yong-Ming AU - Zhou YM FAU - Hu, Ming-Hui AU - Hu MH FAU - Sun, Wei-Ling AU - Sun WL FAU - Xue, Zhi-Zhong AU - Xue ZZ LA - chi PT - English Abstract PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - Zhongguo Shi Yan Xue Ye Xue Za Zhi JT - Zhongguo shi yan xue ye xue za zhi JID - 101084424 RN - 0 (GATA3 Transcription Factor) RN - 0 (GATA3 protein, human) RN - 0 (IL4 protein, human) RN - 0 (STAT4 Transcription Factor) RN - 0 (STAT4 protein, human) RN - 0 (STAT6 Transcription Factor) RN - 0 (STAT6 protein, human) RN - 0 (T-Box Domain Proteins) RN - 0 (T-box transcription factor TBX21) RN - 187348-17-0 (Interleukin-12) RN - 207137-56-2 (Interleukin-4) RN - 82115-62-6 (Interferon-gamma) RN - 83HN0GTJ6D (Cyclosporine) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Anemia, Aplastic/*drug therapy/immunology/metabolism MH - Case-Control Studies MH - Cyclosporine/*pharmacology MH - Female MH - GATA3 Transcription Factor/*metabolism MH - Humans MH - Interferon-gamma/metabolism MH - Interleukin-12/metabolism MH - Interleukin-4/metabolism MH - Male MH - Middle Aged MH - STAT4 Transcription Factor/metabolism MH - STAT6 Transcription Factor/metabolism MH - Signal Transduction MH - T-Box Domain Proteins/*metabolism MH - Th1 Cells/*drug effects MH - Th2 Cells/*drug effects MH - Young Adult EDAT- 2010/12/07 06:00 MHDA- 2011/10/14 06:00 CRDT- 2010/12/07 06:00 PHST- 2010/12/07 06:00 [entrez] PHST- 2010/12/07 06:00 [pubmed] PHST- 2011/10/14 06:00 [medline] AID - 1009-2137(2010)05-1211-09 [pii] PST - ppublish SO - Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010 Oct;18(5):1211-9.