Department of Nutrition, University of Tennessee, Knoxville, TN 37996-1920, USA.
Cell Immunol. 2011;271(2):379-84. doi: 10.1016/j.cellimm.2011.08.004. Epub 2011 Aug 12.
The pro-inflammatory cytokine IL-1β leads to losses in functional β-cell mass in part by inducing the expression of genes that produce soluble mediators of inflammation, such as cyclooxygenase-2 (COX2). In the current study, we sought to understand what factors control the COX2 gene in response to IL-1β and how prostaglandins downstream of COX2 impact pro-inflammatory gene transcription in pancreatic β-cells. We analyzed COX2 gene expression in response to different maneuvers impacting NF-κB proteins. Also, we report alterations in the expression of COX2, EP-3 and EP-4 receptor genes by PGD(2) and PGE(2). Moreover, we examined whether PGD(2) and PGE(2) regulated NF-κB and interferon-gamma activated sequence (GAS) reporter gene activity. IL-1β-mediated induction of the COX2 gene requires the p65 and p50 subunits of NF-κB. In addition, PGD(2) and PGE(2) coordinately alter COX2 and EP receptor gene expression patterns and potentiate the cytokine-mediated transcriptional activity of promoters containing NF-κB or GAS response elements.
促炎细胞因子 IL-1β 通过诱导产生炎症可溶性介质的基因表达（如环氧化酶-2 (COX2)），导致功能性β细胞数量减少。在本研究中，我们试图了解哪些因素控制 COX2 基因对 IL-1β 的反应，以及 COX2 下游的前列腺素如何影响胰腺β细胞中促炎基因的转录。我们分析了 COX2 基因表达对影响 NF-κB 蛋白的不同操作的反应。此外，我们还报告了 PGD(2) 和 PGE(2) 对 COX2、EP-3 和 EP-4 受体基因表达的改变。此外，我们还研究了 PGD(2) 和 PGE(2) 是否调节 NF-κB 和干扰素-γ激活序列 (GAS) 报告基因的活性。IL-1β 介导的 COX2 基因诱导需要 NF-κB 的 p65 和 p50 亚基。此外，PGD(2) 和 PGE(2) 协调改变 COX2 和 EP 受体基因表达模式，并增强含有 NF-κB 或 GAS 反应元件的启动子介导的细胞因子转录活性。
