Upregulation of cIAP2 in regenerating colonocytes in ulcerative colitis.
It has been reported that colonocytes in ulcerative colitis (UC) upregulate anti-apoptotic cytoprotective pathways. An expression-profiling study of apoptosis-related genes suggested that the cellular inhibitor of apoptosis protein-2 (cIAP2) could be upregulated in epithelial cells in UC. The role of cIAP2 in active UC was therefore investigated. Fourteen patients with active UC and 12 control subjects who underwent routine colonoscopy for control of their disease or as part of their examination program for irritable bowel syndrome were included. cIAP1 and cIAP2 expression was investigated by polymerase chain reaction, Western blotting, and immunohistochemistry. The regulation and role of cIAP2 for apoptosis was further investigated in cell cultures. cIAP2, but not cIAP1, was upregulated during active UC in regenerative epithelial cells. A similar upregulation was found in cell lines stimulated with proinflammatory cytokines and was dependent on nuclear factor kappaB activation. Inhibition of cIAP2 increases the susceptibility of epithelial cells to Fas ligation. Inflammation during active UC thus causes an upregulation of cIAP2 in regenerating epithelium, which renders the cells less susceptible to Fas ligation. This might play a role in regeneration of the epithelium but might additionally be implicated in carcinogenesis of UC.
Seidelin
Jakob B
JB
University of Copenhagen, Copenhagen, Denmark. jseidelin@dadlnet.dk
Vainer
Ben
B
Andresen
Lars
L
Nielsen
Ole H
OH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000494:pharmacology; D004338:Drug Combinations; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012038:Regeneration; D044767:Ubiquitin-Protein Ligases; D015854:Up-Regulation
D016207:Cytokines; D004338:Drug Combinations; D053222:Fas Ligand Protein; D051034:Inhibitor of Apoptosis Proteins; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases