Kyttaris Vasileios C, Juang Yuang-Taung, Tenbrock Klaus, Weinstein Arthur, Tsokos George C
Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
J Immunol. 2004 Sep 1;173(5):3557-63. doi: 10.4049/jimmunol.173.5.3557.
T cells from patients with systemic lupus erythematosus express increased levels of the cAMP response element modulator (CREM) that has been shown to bind to the IL-2 promoter and suppress its activity. In this study, we demonstrate that CREM binds to the proximal promoter of the c-fos proto-oncogene in live systemic lupus erythematosus T cells and represses its expression following stimulation in vitro. Decreased levels of c-fos protein result in decreased AP-1 activity, as determined in shift assays. Blockade of the translation of CREM mRNA with an antisense CREM vector increases the expression of c-fos and the AP-1 activity. The levels of c-fos mRNA vary with disease activity. We conclude that CREM represses the expression of c-fos and limits the activity of the enhancer AP-1. Thus, CREM is involved indirectly in the modulation of transcriptional regulation of multiple genes including IL-2.
系统性红斑狼疮患者的T细胞中，环磷酸腺苷反应元件调节因子（CREM）的表达水平升高，该调节因子已被证明可与白细胞介素-2（IL-2）启动子结合并抑制其活性。在本研究中，我们证明CREM可与活体系统性红斑狼疮T细胞中c-fos原癌基因的近端启动子结合，并在体外刺激后抑制其表达。如迁移实验所示，c-fos蛋白水平降低导致激活蛋白-1（AP-1）活性下降。用反义CREM载体阻断CREM mRNA的翻译可增加c-fos的表达和AP-1活性。c-fos mRNA水平随疾病活动而变化。我们得出结论，CREM可抑制c-fos的表达并限制增强子AP-1的活性。因此，CREM间接参与包括IL-2在内的多个基因转录调控的调节。
