Yudina Yulyana, Parhamifar Ladan, Bengtsson Astrid M-L, Juhas Maria, Sjölander Anita
Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, CRC, Entrance 72, Building 91, Floor 11, SE-205 02 Malmö, Sweden.
Prostaglandins Leukot Essent Fatty Acids. 2008 Dec;79(6):223-31. doi: 10.1016/j.plefa.2008.09.024.
In this study the mRNA and protein levels of the key enzymes involved in eicosanoid biosynthesis and the cysteinyl leukotriene receptors (CysLT1R and CysLT2R) have been analysed in non-transformed intestinal epithelial and colon cancer cell lines. Our results revealed that tumour necrosis factor alpha (TNF-alpha), and leukotriene D4 (LTD4), which are inflammatory mediators implicated in carcinogenesis, stimulated an increase of cyclooxygenase-2 (COX-2), in non-transformed epithelial cells, and 5-lipoxygenase (5-LO) in both non-transformed and cancer cell lines. Furthermore, these mediators also stimulated an up-regulation of LTC4 synthase in cancer cells as well as non-transformed cells. We also observed an endogenous production of CysLTs in these cells. TNF-alpha and LTD4, to a lesser extent, up-regulate the CysLT1R levels. Interestingly, TNF-alpha also reduced CysLT2R expression in cancer cells. Our results demonstrate that inflammatory mediators can cause intestinal epithelial cells to up-regulate the expression of enzymes needed for the biosynthesis of eicosanoids, including the cysteinyl leukotrienes, as well as the signal transducing proteins, the CysLT receptors, thus providing important mechanisms for both maintaining inflammation and for tumour progression.
在本研究中，我们分析了非转化肠上皮细胞系和结肠癌细胞系中参与类二十烷酸生物合成的关键酶以及半胱氨酰白三烯受体（CysLT1R和CysLT2R）的mRNA和蛋白质水平。我们的结果显示，肿瘤坏死因子α（TNF-α）和白三烯D4（LTD4）作为参与致癌作用的炎症介质，在非转化上皮细胞中刺激了环氧合酶-2（COX-2）的增加，在非转化细胞系和癌细胞系中均刺激了5-脂氧合酶（5-LO）的增加。此外，这些介质还刺激了癌细胞以及非转化细胞中白三烯C4合成酶的上调。我们还观察到这些细胞中半胱氨酰白三烯的内源性产生。TNF-α和LTD4在较小程度上上调了CysLT1R水平。有趣的是，TNF-α还降低了癌细胞中CysLT2R的表达。我们的结果表明，炎症介质可导致肠上皮细胞上调类二十烷酸生物合成所需的酶的表达，包括半胱氨酰白三烯，以及信号转导蛋白即CysLT受体，从而为维持炎症和肿瘤进展提供重要机制。
