Colon Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Colon Cancer, including details on causes, treatment, symptoms.

Up-regulation of cyclooxygenase-2 by interleukin-1beta in colon carcinoma cells.

Duque J, Díaz-Muñoz MD, Fresno M, Iñiguez MA

Centro de Biología Molecular "Severo Ochoa", Departamento de Biología Molecular, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.

Growing evidence shows that Interleukin (IL)-1beta and Cyclooxygenase 2 (COX-2) play a crucial role in the pathogenesis of inflammatory diseases and tumor growth, particularly in the gastrointestinal tract. Here, we have analyzed the regulation of COX-2 by IL-1beta in the human colon carcinoma cell line Caco-2, showing that COX-2 induction by this cytokine is due to both nuclear factor (NF)-kappaB-dependent transcriptional and p38 mitogen-activated protein kinase (MAPK)-mediated post-transcriptional mechanisms. Treatment of these cells with IL-1beta increased the levels of COX-2 mRNA and protein and hence the production of PGE2. IL-1beta induced NF-kappaB activation in Caco-2 cells, promoting the binding of this transcription factor to DNA and increasing NF-kappaB-dependent transcription. Inhibition of NF-kappaB activation diminished IL-1beta-mediated transcriptional activation of COX-2. Furthermore, mutation or deletion of a putative NF-kappaB binding site in the human COX-2 promoter greatly diminished its induction by IL-1beta. In addition, this cytokine induced a rapid increase in p38 MAPK activation. Interestingly, inhibition of p38 MAPK by SB203580 severely decreased induction of COX-2 expression by IL-1beta. p38 MAPK signalling was required for IL-1beta-dependent stabilization of COX-2 transcript. Given the importance of COX-2 expression in intestinal inflammation and colon carcinogenesis, these findings contribute to determine the key signalling pathways involved in the regulation of COX-2 expression in colorectal cells by inflammatory stimuli, such as IL-1beta.

Published 15 May 2006 in Cell Signal, 18(8): 1262-9.
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