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

Increased sensitivity to TRAIL-induced apoptosis occurs during the adenoma to carcinoma transition of colorectal carcinogenesis

“…Increased sensitivity to TRAIL during carcinogenesis is not a feature of all tissues; for example, comparisons of the response of normal and malignant ovarian cells to TRAIL have shown normal cells to be sensitive to TRAIL whereas cells from different ovarian carcinomas varied in their responses (Lane et al, 2004). Normal colonocytes have previously been reported to be relatively resistant to TRAILinduced apoptosis compared to colorectal carcinoma cells: normal human colonic epithelial cells did not undergo apoptosis in response to 0.1 mg ml À1 TRAIL, but COLO205 colon carcinoma cells were sensitive to this concentration (Sträter et al, 2002b). Koornstra et al (2003) reported that colonic tumours overexpressed the TRAIL receptors TRAIL-R1 and TRAIL-R2 in vivo relative to normal mucosa, but that overall expression of TRAIL receptors was not significantly different between adenomas and carcinomas.…”

“…Normal colonocytes cultured as intact crypts embedded in collagen have previously been reported to be relatively resistant to TRAIL-induced apoptosis compared to colorectal carcinoma cells (Sträter et al, 2002b), but it is not known whether the sensitivity to TRAIL is acquired early or late in colorectal carcinogenesis, since the response of premalignant adenoma cells to TRAIL has never been examined. Koornstra et al (2003) showed that, in vivo, cytoplasmic TRAIL-R1 and -R2 expression was higher in both adenomas and carcinomas compared to normal colonic epithelium; however, there were no further changes in expression of either TRAIL receptors or decoy receptors between adenomas and carcinomas.…”

TNF-Related Apoptosis-Inducing Ligand Death Pathway-Mediated Human Beta-Cell Destruction

“…We used two T-cell clones, CD4 + THINSB1 and CD8 + THINSB2 for this study. These clones were derived from a new-onset Type I diabetic patient whose T cells responded well to beta-cell antigenic peptide INSB (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23) [33,34,35]. Patient informed consent was obtained from the patient and patient's parents.…”

“…INSB (13)(14)(15)(16)(17)(18)(19)(20)(21) and INSB (12)(13)(14)(15)(16)(17)(18)(19)(20) are the minimal epitopes of cloned THINSB1 cells and THINSB2 cells respectively. The T-cell clones THINSB1 and THINSB2 were maintained in culture by stimulating 2×10 5 cell at weekly intervals with the specific peptides INSB(9-23) and INSB (12)(13)(14)(15)(16)(17)(18)(19)(20) respectively at 10 µmol/l in complete RPMI 1640 medium containing 5% Lymphocult-T-LF (Biotest, Dreieich, Germany), 50 U/ml human recombinant interneukin-2 (rIL-2) (GIBCO, Missisauga, Ontario, Canada), and γ-irradiated (3000 rad) autologous peripheral blood mononuclear cells (PBMC) (2×10 6 /ml) [33,34]. Phytohemagglutinin (PHA, SIGMA) and anti-CD3 mAb (BD PharMingen) were used to activate T cells from the same donor of T-cell clones for controls.…”

“…These events that subsequently lead to the activation of the caspase cascade [8,15,16]. In contrast with TRAIL-R1 and TRAIL-R2, TRAIL-R3/decoy receptor (DcR) 1 exists as a glycosyl-phosphatidylinositol-anchored surface protein that is not able to signal cell death, thus acting as a decoy receptor [11,13,15,16,17,18,19]. A fourth TRAIL receptor, TRAIL-R4/DcR2, contains only a partial death domain and does not mediate apoptosis upon binding of TRAIL.…”