title: TRAIL receptor deficiency sensitizes mice to dextran sodium sulphate-induced colitis and colitis-associated carcinogenesis.
abstract: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor (TRAIL-R) play important roles in immune regulation and cancer cell death. Although TRAIL has been shown to induce chemokine release in various tumour cells, the function of TRAIL-R in the development of colitis and colitis-associated carcinogenesis has not been explored. In this study, we found that TRAIL-R-deficient mice exhibited a higher incidence of colitis and colitis-associated cancer than that of wild-type (WT) mice, and TRAIL-R expression was down-regulated in WT mice that were fed dextran sulphate sodium. Chemokines, including CCL2 and CXCL1, were highly expressed in the serum and inflammatory colon tissues of TRAIL-R(-/-) mice compared with WT mice, and TRAIL-R(-/-) mice showed a marked infiltration of immune cells during colitis. Hyperactivation of Janus kinase and nuclear factor-κB in colon epithelial cells was also observed, which correlated with the severity of colonic inflammation in TRAIL-R(-/-) mice. These data suggest that TRAIL-R plays a protective role in chemical-induced colon injury and negatively regulates mucosal immune responses.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Jieqing
authors.initials: J
authors.lastname: Zhu
authors.forename: Longfei
authors.initials: L
authors.lastname: Chen
authors.forename: Juan
authors.initials: J
authors.lastname: Shi
authors.forename: Shilian
authors.initials: S
authors.lastname: Liu
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Liu
authors.forename: Dexian
authors.initials: D
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000032:analysis; D054360:Chemokine CXCL1 / Q000032:analysis; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000517:prevention & control*; D003110:Colonic Neoplasms / Q000209:etiology*; D016264:Dextran Sulfate; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000502:physiology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000172:deficiency / Q000502:physiology*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D016328:NF-kappa B; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D016264:Dextran Sulfate; D048031:JNK Mitogen-Activated Protein Kinases
keywords: colitis; colitis-associated cancer; inflammation; tumour necrosis factor-related apoptosis-inducing ligand receptor