Interleukin 1 and interleukin 1 beta converting enzyme (caspase 1) expression in the human colonic epithelial barrier. Caspase 1 downregulation in colon cancer

Background-Interleukin (IL) 1 beta converting enzyme (now known as caspase 1) is able to process pro-IL-1 beta into its active form and is involved in proapoptotic signalling. Aims-To characterise IL-1 and caspase 1 expression in human colonic epithel ial cells. Methods-Intracellular IL-1 content (IL-1 alpha and IL-1 beta) was measured by ELISA in freshly isolated human normal colonocytes. Caspase 1 expression was determined both at the mRNA level using in situ hybridisation and reve rse transcription polymerase chain reaction, and at the protein level by im munoblotting experiments using antibodies specific for the preform of caspa se 1 and for its cleavage forms. Results-Low amounts of IL-1 beta were found in nearly all preparations (92% ), and IL-1 alpha was detected in only 45% of human colonocyte preparations . The normal colonic epithelium strongly expressed caspase 1, both at the m RNA level and at the protein level in its latent form. In contrast, caspase 1 was not expressed in colon cancer (primary colonic adenocarcinomas and c ancer cell lines). Conclusions-The demonstration that the human colonic epithelial barrier is able to express caspase 1 and its substrate IL-1 beta reinforces the concep t that, under certain conditions, the epithelium could trigger an inflammat ory reaction. In addition, the finding that caspase 1 was downregulated in colonic adenocarcinomas supports the concept that disrupted apoptosis pathw ays may be involved in tumour formation and/or may confer resistance to tre atment.