TRAIL and its receptors in the colonic epithelium: A putative role in the defense of viral infections

Background & Aims: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family and induces apoptosis by cross-linking either of the 2 TRAIL receptors containing a death domain (TRAIL-R1 or TRAIL-R2). TRAIL-R3 and TRAIL-R4 are receptors that do not transmit an apoptotic signal. The aim of this study was to investigate the expression and function of TRAIL and its receptors in normal colonic epithelium. Methods: TRAIL and TRAIL receptor expression was studied by reverse-transcriptase polymerase chain reaction and immunohistochemistry. TRAIL sensitivity of epithelial cells was determined in vitro. Results: Normal colonic epithelial cells express TRAIL, TRAIL-R1, TRAIL-R2, and TRAIL-R4. Interestingly, TRAIL and TRAIL-R2 are coexpressed mostly in the luminal surface epithelium. Despite the expression of apoptosis-mediating TRAIL receptors, the normal colonic crypt epithelium is completely resistant to TRAIL-induced apoptosis in vitro. Using an infection model with restricted human cytomegalovirus gene expression or productive adenovirus infection in the colon carcinoma cell line Caco-2, we show that TRAIL sensitivity of colonic epithelial cells is induced on virus infection along with an up-regulation of TRAIL-R1 and TRAIL-R2 on the cell surface. Conclusions: We conclude that the TRAIL system may play a role in the early elimination of virus-infected epithelial cells in the normal gut.