Interleukin-1β up-regulates the expression of thrombopoietin and transcription factors c-Jun, c-Fos, GATA-1, and NF-E2 in megakaryocytic cells
Interleukin-1β up-regulates the expression of thrombopoietin and transcription factors c-Jun, c-Fos, GATA-1, and NF-E2 in megakaryocytic cells
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DOI：
10.1016/j.lab.2003.09.006
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发表时间：
2004-02-01
期刊：
影响因子：
--
通讯作者：
Yuen, PMP
中科院分区：
文献类型：
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作者：
Chuen, CKY;Li, K;Yuen, PMP
多功能细胞因子白细胞介素-1 β（IL-1 β）在机体的免疫和炎症反应中起着重要作用。IL-1 β对血小板增多和巨核细胞生成的作用机制仍存在争议。在以前的报道中，我们已经证明了IL-1受体（IL-1 RI和IL-1 RII）的表达和IL-1 β对原代人巨核细胞（MK）的增强作用。在这项研究中，我们研究了IL-1 β对MK细胞系CHRF和Meg-01中血小板生成素（TPO）和转录因子c-Jun、c-Fos、加塔-1和p45核因子-E2（NF-E2）表达的可能直接影响。我们的研究结果表明，IL-1 β以剂量和时间依赖性方式上调这些转录因子的信使RNA（mRNA）和蛋白表达。在CHRF细胞中，mRNA：c-Jun（3.4倍，在15分钟时达到峰值），c-Fos（4.2倍，15分钟），加塔-1（4.0倍，60分钟），NF-E2（3.2倍，120分钟）和蛋白质表达：IL-1 β处理后c-Jun（3.0倍，30分钟）、c-Fos（1.7倍，30分钟）、加塔-1（11.5倍，60分钟）、NF-E2（12.5倍，120分钟）明显增强。对IL-1 β的反应在总细胞和核提取物中是一致的，并且通过用放线菌素D或放线菌酮预处理而显著降低。IL-1受体拮抗剂（IL-1 RA）抑制IL-1 β对这些转录因子的刺激作用高达78%。在IL-1 β刺激下，TPO表达增加了9.9倍以上。TPO中和抗体并没有显著降低IL-1 β的作用。结论：IL-1 β上调MK细胞TPO、c-Jun、c-Fos、加塔-1和NF-E2的表达。其机制可能是由IL-1 β受体介导的，并需要转录或蛋白质合成。IL-1 β在MK谱系中的直接参与可能为炎症反应期间的血小板增多现象提供了解释。
The multifunctional cytokine interleukin-1beta (IL-1beta) plays a central role in the body's immune and inflammatory responses. The mechanism of IL-1beta on thrombocytosis and megakaryocytopoiesis has remained controversial. In previous reports, we have demonstrated the expression of IL-1 receptors (IL-1RI and IL-1RII) and enhancing effects of IL-1beta on primary human megakaryocytic (MK) cells. In this study, we investigated the possible direct effects of IL-1beta on the expression of thrombopoietin (TPO) and transcription factors c-Jun, c-Fos, GATA-1, and p45 nuclear factor-E2 (NF-E2) in MK cell lines CHRF and Meg-01. Our results demonstrated that IL-1beta up-regulated messenger RNA (mRNA) and protein expressions of these transcription factors in a dose- and time-dependent manner. In CHRF cells, mRNA: c-Jun (3.4-fold, peaked at 15 minutes), c-Fos (4.2-fold, 15 minutes), GATA-1 (4.0-fold, 60 minutes), NF-E2 (3.2-fold, 120 minutes) and protein expression: c-Jun (3.0-fold, 30 minutes), c-Fos (1.7-fold, 30 minutes), GATA-1 (11.5-fold, 60 minutes), NF-E2 (12.5-fold, 120 minutes) were evidently enhanced after treatment with IL-1beta. The response to IL-1beta was consistent in the total cell and nuclear extracts and was significantly reduced by pretreatment with actinomycin D or cycloheximide. An IL-1-receptor antagonist (IL-1RA) inhibited the stimulatory effects of IL-1beta on these transcription factors by as much as 78%. TPO expression was increased by more than 9.9-fold on stimulation with IL-1beta. A TPO-neutralizing antibody did not significantly reduce the effects of IL-1beta. We conclude that IL-1beta up-regulates the expression of TPO, c-Jun, c-Fos, GATA-1, and NF-E2 in MK cells. The mechanism might be mediated by IL-1beta receptors and require transcription or protein synthesis. The direct involvement of IL-1beta in the MK lineage may provide an explanation for the phenomenon of thrombocytosis during inflammatory responses.