Downregulation of T-bet/GATA-3 ratio induced by IL-11 treatment is responsible for Th1/Th2 balance restoration in human immune thrombocytopenic purpura (ITP)
| Autor: | Muqing He, Xiaoji Lin, Xieming Zhou, Ying Lin, Limin Jin, Rongxin Yao, Yunhua Bao, Xiahui Pan, Wenjian Guo, Baoling Zhu, Qianqian Li |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male medicine.medical_specialty Cellular immunity GATA3 Transcription Factor Peripheral blood mononuclear cell Pathogenesis Immune system Th2 Cells Downregulation and upregulation immune system diseases hemic and lymphatic diseases Internal medicine Medicine Humans Purpura Thrombocytopenic Idiopathic Hematology Dose-Response Relationship Drug business.industry hemic and immune systems Th1 Cells medicine.disease Interleukin-11 Thrombocytopenic purpura Endocrinology Gene Expression Regulation Th1-Th2 Balance Immunology Female Cardiology and Cardiovascular Medicine business T-Box Domain Proteins |
| Zdroj: | Journal of thrombosis and thrombolysis. 38(2) |
| ISSN: | 1573-742X |
| Popis: | Abnormal cellular immunity induced by deranged Th1/Th2 profile has been revealed to play a critical role in the pathogenesis of immune thrombocytopenic purpura (ITP). Correction of the shifted Th1/Th2 balance represents a potential therapeutic approach to treat ITP. Here, we investigated the effects of IL-11 on the restoration of Th1/Th2 balance in the peripheral blood mononuclear cells (PBMCs) isolated from adult ITP patients. As shown here, we observed a higher ratio of T-bet/GATA-3 gene expression by quantitative real-time PCR in the PBMCs from ITP patients, consistent with the presence of an abnormally high Th1/Th2 ratio. Remarkably, upon IL-11 treatment, a reversal of T-bet/GATA-3 ratio in ITP was achieved and was shown to be responsible for the restoration of Th1/Th2 balance, with IL-11 at 100 ng/ml demonstrating the highest efficiency. T-bet and GATA-3 are the two transcriptional factors that have been indicated to be the master regulators for Th1 and Th2 lineage commitment, respectively. In the presence of 100 ng/ml IL-11, GATA-3 transcript abundance rose up to ~85-fold of that measured in untreated cells, whereas T-bet transcripts were lowered merely to ~41 %, suggesting that GATA-3 was the major contributor for the reversal of T-bet/GATA-3 ratio. Thus, our findings may very well encourage the development of novel medicines that specifically target and correct the T-bet/GATA-3 imbalance identified in ITP. |
| Databáze: | OpenAIRE |
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