Leukotriene D₄ induces AP-1 but not NFκB signaling in intestinal epithelial cells

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• 作者：Astrid M.-L. Bengtsson ; Ramin Massoumi ; Anita Sj&#xf6 ; l ; er
• 关键词：Cysteinyl leukotrienes ; CysLT₁R ; Colon cancer ; Inflammation ; Epithelial cells ; AP-1 ; NFκ ; B
• 刊名：Prostaglandins and Other Lipid Mediators
• 出版年：2008
• 出版时间：March 2008
• 年：2008
• 卷：85
• 期：3-4
• 页码：100-106
• 全文大小：557 K

文摘

We have previously shown that leukotriene D₄ (LTD₄), a known pro-inflammatory mediator, induces increased survival and proliferation of intestinal epithelial cells. In this study we examined whether LTD₄ functions via activation of the transcription factors NFκB and AP-1, which are potent inducers of mitogenesis. We found that the NFκB inhibitory protein IκBα was not degraded upon LTD₄ stimulation. Furthermore, nuclear translocation of the classical p65 or alternative p52 subunits of NFκB was not observed. Accordingly, LTD₄ stimulation failed to induce NFκB transcriptional activity. Instead we found that LTD₄ induced phosphorylation of c-Jun-N-terminal kinase (JNK) and transcriptional activity of AP-1, which could be reduced by a JNK inhibitor. Moreover, LTD₄ induced cell proliferation, and this effect was also blocked upon addition of a JNK inhibitor. Our findings show for the first time that JNK/AP-1 but not NFκB is a downstream target of LTD₄ in intestinal epithelial cells, suggesting that AP-1 is an important mediator of LTD₄-induced mitogenic effects.