Regulation of the eicosanoid pathway by tumour necrosis factor alpha and leukotriene D4 in intestinal epithelial cells.

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.

Leukotriene D(4) induces AP-1 but not NFkappaB signaling in intestinal epithelial cells.

We have previously shown that leukotriene D(4) (LTD(4)), a known pro-inflammatory mediator, induces increased survival and proliferation of intestinal epithelial cells. In this study we examined whether LTD(4) functions via activation of the transcription factors NFkappaB and AP-1, which are potent inducers of mitogenesis. We found that the NFkappaB inhibitory protein IkappaBalpha was not degraded upon LTD(4) stimulation.