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Published in: Virchows Archiv 6/2007

01-12-2007 | Original Article

Upregulation of cIAP2 in regenerating colonocytes in ulcerative colitis

Authors: Jakob B. Seidelin, Ben Vainer, Lars Andresen, Ole H. Nielsen

Published in: Virchows Archiv | Issue 6/2007

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Abstract

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 κB 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.
Literature
1.
go back to reference Andresen L, Jorgensen VL, Perner A, Hansen A, Eugen-Olsen J, Rask-Madsen J (2005) Activation of nuclear factor kappaB in colonic mucosa from patients with collagenous and ulcerative colitis. Gut 54:503–509PubMedCrossRef Andresen L, Jorgensen VL, Perner A, Hansen A, Eugen-Olsen J, Rask-Madsen J (2005) Activation of nuclear factor kappaB in colonic mucosa from patients with collagenous and ulcerative colitis. Gut 54:503–509PubMedCrossRef
2.
go back to reference Bojarski C, Gitter AH, Bendfeldt K, Mankertz J, Schmitz H, Wagner S, Fromm M, Schulzke JD (2001) Permeability of human HT-29/B6 colonic epithelium as a function of apoptosis. J Physiol 535:541–552PubMedCrossRef Bojarski C, Gitter AH, Bendfeldt K, Mankertz J, Schmitz H, Wagner S, Fromm M, Schulzke JD (2001) Permeability of human HT-29/B6 colonic epithelium as a function of apoptosis. J Physiol 535:541–552PubMedCrossRef
3.
go back to reference Brauchle M, Madlener M, Wagner AD, Angermeyer K, Lauer U, Hofschneider PH, Gregor M, Werner S (1996) Keratinocyte growth factor is highly overexpressed in inflammatory bowel disease. Am J Pathol 149:521–529PubMed Brauchle M, Madlener M, Wagner AD, Angermeyer K, Lauer U, Hofschneider PH, Gregor M, Werner S (1996) Keratinocyte growth factor is highly overexpressed in inflammatory bowel disease. Am J Pathol 149:521–529PubMed
4.
go back to reference Chang CS, Chen WN, Lin HH, Wu CC, Wang CJ (2004) Increased oxidative DNA damage, inducible nitric oxide synthase, nuclear factor kappaB expression and enhanced antiapoptosis-related proteins in Helicobacter pylori-infected non-cardiac gastric adenocarcinoma. World J Gastroenterol 10:2232–2240PubMed Chang CS, Chen WN, Lin HH, Wu CC, Wang CJ (2004) Increased oxidative DNA damage, inducible nitric oxide synthase, nuclear factor kappaB expression and enhanced antiapoptosis-related proteins in Helicobacter pylori-infected non-cardiac gastric adenocarcinoma. World J Gastroenterol 10:2232–2240PubMed
5.
go back to reference Chu ZL, McKinsey TA, Liu L, Gentry JJ, Malim MH, Ballard DW (1997) Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis c-IAP2 is under NF-kappaB control. Proc Natl Acad Sci USA 94:10057–10062PubMedCrossRef Chu ZL, McKinsey TA, Liu L, Gentry JJ, Malim MH, Ballard DW (1997) Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis c-IAP2 is under NF-kappaB control. Proc Natl Acad Sci USA 94:10057–10062PubMedCrossRef
6.
go back to reference Conte D, Holcik M, Lefebvre CA, Lacasse E, Picketts DJ, Wright KE, Korneluk RG (2006) Inhibitor of apoptosis protein cIAP2 is essential for lipopolysaccharide-induced macrophage survival. Mol Cell Biol 26:699–708PubMedCrossRef Conte D, Holcik M, Lefebvre CA, Lacasse E, Picketts DJ, Wright KE, Korneluk RG (2006) Inhibitor of apoptosis protein cIAP2 is essential for lipopolysaccharide-induced macrophage survival. Mol Cell Biol 26:699–708PubMedCrossRef
7.
go back to reference Eaden JA, Abrams KR, Mayberry JF (2001) The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 48:526–535PubMedCrossRef Eaden JA, Abrams KR, Mayberry JF (2001) The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 48:526–535PubMedCrossRef
8.
9.
go back to reference Fenoglio-Preiser C, Noffsinger AE, Stemmermann G, Lantz P, Lindstrom M (1999) Ulcerative colitis. Gastrointestinal pathology—an atlas and text. Lippincott Williams & Wilkins, Philadelphia, pp 659–682 Fenoglio-Preiser C, Noffsinger AE, Stemmermann G, Lantz P, Lindstrom M (1999) Ulcerative colitis. Gastrointestinal pathology—an atlas and text. Lippincott Williams & Wilkins, Philadelphia, pp 659–682
10.
go back to reference Gitter AH, Bendfeldt K, Schulzke JD, Fromm M (2000) Leaks in the epithelial barrier caused by spontaneous and TNF-alpha-induced single-cell apoptosis. FASEB J 14:1749–1753PubMedCrossRef Gitter AH, Bendfeldt K, Schulzke JD, Fromm M (2000) Leaks in the epithelial barrier caused by spontaneous and TNF-alpha-induced single-cell apoptosis. FASEB J 14:1749–1753PubMedCrossRef
11.
go back to reference Gitter AH, Wullstein F, Fromm M, Schulzke JD (2001) Epithelial barrier defects in ulcerative colitis: characterization and quantification by electrophysiological imaging. Gastroenterology 121:1320–1328PubMedCrossRef Gitter AH, Wullstein F, Fromm M, Schulzke JD (2001) Epithelial barrier defects in ulcerative colitis: characterization and quantification by electrophysiological imaging. Gastroenterology 121:1320–1328PubMedCrossRef
12.
go back to reference Gordon GJ, Mani M, Mukhopadhyay L, Dong L, Yeap BY, Sugarbaker DJ, Bueno R (2007) Inhibitor of apoptosis proteins are regulated by tumour necrosis factor-alpha in malignant pleural mesothelioma. J Pathol 211:439–446PubMedCrossRef Gordon GJ, Mani M, Mukhopadhyay L, Dong L, Yeap BY, Sugarbaker DJ, Bueno R (2007) Inhibitor of apoptosis proteins are regulated by tumour necrosis factor-alpha in malignant pleural mesothelioma. J Pathol 211:439–446PubMedCrossRef
13.
go back to reference Heinen CD, Noffsinger AE, Belli J, Straughen J, Fischer J, Groden J, Fenoglio-Preiser CM (1997) Regenerative lesions in ulcerative colitis are characterized by microsatellite mutation. Genes Chromosomes Cancer 19:170–175PubMedCrossRef Heinen CD, Noffsinger AE, Belli J, Straughen J, Fischer J, Groden J, Fenoglio-Preiser CM (1997) Regenerative lesions in ulcerative colitis are characterized by microsatellite mutation. Genes Chromosomes Cancer 19:170–175PubMedCrossRef
14.
go back to reference Hiribarren A, Heyman M, L’Helgouac’h A, Desjeux JF (1993) Effect of cytokines on the epithelial function of the human colon carcinoma cell line HT29 cl 19A. Gut 34:616–620PubMedCrossRef Hiribarren A, Heyman M, L’Helgouac’h A, Desjeux JF (1993) Effect of cytokines on the epithelial function of the human colon carcinoma cell line HT29 cl 19A. Gut 34:616–620PubMedCrossRef
15.
go back to reference Iwamoto M, Koji T, Makiyama K, Kobayashi N, Nakane PK (1996) Apoptosis of crypt epithelial cells in ulcerative colitis. J Pathol 180:152–159PubMedCrossRef Iwamoto M, Koji T, Makiyama K, Kobayashi N, Nakane PK (1996) Apoptosis of crypt epithelial cells in ulcerative colitis. J Pathol 180:152–159PubMedCrossRef
16.
go back to reference Koshiji M, Adachi Y, Sogo S, Taketani S, Oyaizu N, Than S, Inaba M, Phawa S, Hioki K, Ikehara S (1998) Apoptosis of colorectal adenocarcinoma (COLO 201) by tumour necrosis factor-alpha (TNF-alpha) and/or interferon-gamma (IFN-gamma), resulting from down-modulation of Bcl-2 expression. Clin Exp Immunol 111:211–218PubMedCrossRef Koshiji M, Adachi Y, Sogo S, Taketani S, Oyaizu N, Than S, Inaba M, Phawa S, Hioki K, Ikehara S (1998) Apoptosis of colorectal adenocarcinoma (COLO 201) by tumour necrosis factor-alpha (TNF-alpha) and/or interferon-gamma (IFN-gamma), resulting from down-modulation of Bcl-2 expression. Clin Exp Immunol 111:211–218PubMedCrossRef
17.
go back to reference Langholz E (1999) Ulcerative colitis. An epidemiological study based on a regional inception cohort, with special reference to disease course and prognosis. Dan Med Bull 46:400–415PubMed Langholz E (1999) Ulcerative colitis. An epidemiological study based on a regional inception cohort, with special reference to disease course and prognosis. Dan Med Bull 46:400–415PubMed
18.
go back to reference Langholz E, Munkholm P, Davidsen M, Binder V (1994) Course of ulcerative colitis: analysis of changes in disease activity over years. Gastroenterology 107:3–11PubMed Langholz E, Munkholm P, Davidsen M, Binder V (1994) Course of ulcerative colitis: analysis of changes in disease activity over years. Gastroenterology 107:3–11PubMed
19.
go back to reference Liston P, Fong WG, Korneluk RG (2003) The inhibitors of apoptosis: there is more to life than Bcl2. Oncogene 22:8568–8580PubMedCrossRef Liston P, Fong WG, Korneluk RG (2003) The inhibitors of apoptosis: there is more to life than Bcl2. Oncogene 22:8568–8580PubMedCrossRef
20.
go back to reference Liu Z, Li H, Derouet M, Berezkin A, Sasazuki T, Shirasawa S, Rosen K (2006) Oncogenic Ras inhibits anoikis of intestinal epithelial cells by preventing the release of a mitochondrial pro-apoptotic protein Omi/HtrA2 into the cytoplasm. J Biol Chem 281:14738–14747PubMedCrossRef Liu Z, Li H, Derouet M, Berezkin A, Sasazuki T, Shirasawa S, Rosen K (2006) Oncogenic Ras inhibits anoikis of intestinal epithelial cells by preventing the release of a mitochondrial pro-apoptotic protein Omi/HtrA2 into the cytoplasm. J Biol Chem 281:14738–14747PubMedCrossRef
21.
go back to reference Liu Z, Li H, Derouet M, Filmus J, LaCasse EC, Korneluk RG, Kerbel RS, Rosen KV (2005) ras Oncogene triggers up-regulation of cIAP2 and XIAP in intestinal epithelial cells: epidermal growth factor receptor-dependent and -independent mechanisms of ras-induced transformation. J Biol Chem 280:37383–37392PubMedCrossRef Liu Z, Li H, Derouet M, Filmus J, LaCasse EC, Korneluk RG, Kerbel RS, Rosen KV (2005) ras Oncogene triggers up-regulation of cIAP2 and XIAP in intestinal epithelial cells: epidermal growth factor receptor-dependent and -independent mechanisms of ras-induced transformation. J Biol Chem 280:37383–37392PubMedCrossRef
22.
go back to reference Liu Z, Li H, Wu X, Yoo BH, Yan SR, Stadnyk AW, Sasazuki T, Shirasawa S, LaCasse EC, Korneluk RG, Rosen KV (2006) Detachment-induced upregulation of XIAP and cIAP2 delays anoikis of intestinal epithelial cells. Oncogene 25:7680–7690PubMedCrossRef Liu Z, Li H, Wu X, Yoo BH, Yan SR, Stadnyk AW, Sasazuki T, Shirasawa S, LaCasse EC, Korneluk RG, Rosen KV (2006) Detachment-induced upregulation of XIAP and cIAP2 delays anoikis of intestinal epithelial cells. Oncogene 25:7680–7690PubMedCrossRef
23.
go back to reference Lundberg JO, Hellstrom PM, Lundberg JM, Alving K (1994) Greatly increased luminal nitric oxide in ulcerative colitis. Lancet 344:1673–1674PubMedCrossRef Lundberg JO, Hellstrom PM, Lundberg JM, Alving K (1994) Greatly increased luminal nitric oxide in ulcerative colitis. Lancet 344:1673–1674PubMedCrossRef
24.
go back to reference Madara JL, Stafford J (1989) Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers. J Clin Invest 83:724–727PubMedCrossRef Madara JL, Stafford J (1989) Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers. J Clin Invest 83:724–727PubMedCrossRef
25.
go back to reference McKaig BC, Hughes K, Tighe PJ, Mahida YR (2002) Differential expression of TGF-beta isoforms by normal and inflammatory bowel disease intestinal myofibroblasts. Am J Physiol Cell Physiol 282:C172–C182PubMed McKaig BC, Hughes K, Tighe PJ, Mahida YR (2002) Differential expression of TGF-beta isoforms by normal and inflammatory bowel disease intestinal myofibroblasts. Am J Physiol Cell Physiol 282:C172–C182PubMed
26.
go back to reference Naujokat C, Sezer O, Possinger K (1999) Tumor necrosis factor-alpha and interferon-gamma induce expression of functional Fas ligand on HT29 and MCF7 adenocarcinoma cells. Biochem Biophys Res Commun 264:813–819PubMedCrossRef Naujokat C, Sezer O, Possinger K (1999) Tumor necrosis factor-alpha and interferon-gamma induce expression of functional Fas ligand on HT29 and MCF7 adenocarcinoma cells. Biochem Biophys Res Commun 264:813–819PubMedCrossRef
27.
go back to reference O’Connell J, Bennett MW, Nally K, O’Sullivan GC, Collins JK, Shanahan F (2000) Interferon-gamma sensitizes colonic epithelial cell lines to physiological and therapeutic inducers of colonocyte apoptosis. J Cell Physiol 185:331–338PubMedCrossRef O’Connell J, Bennett MW, Nally K, O’Sullivan GC, Collins JK, Shanahan F (2000) Interferon-gamma sensitizes colonic epithelial cell lines to physiological and therapeutic inducers of colonocyte apoptosis. J Cell Physiol 185:331–338PubMedCrossRef
28.
29.
go back to reference Roos W, Baumgartner M, Kaina B (2004) Apoptosis triggered by DNA damage O6-methylguanine in human lymphocytes requires DNA replication and is mediated by p53 and Fas/CD95/Apo-1. Oncogene 23:359–367PubMedCrossRef Roos W, Baumgartner M, Kaina B (2004) Apoptosis triggered by DNA damage O6-methylguanine in human lymphocytes requires DNA replication and is mediated by p53 and Fas/CD95/Apo-1. Oncogene 23:359–367PubMedCrossRef
30.
go back to reference Ruemmele FM, Beaulieu JF, O’Connell J, Bennett MW, Seidman EG, Lentze MJ (2002) The susceptibility to Fas-induced apoptosis in normal enterocytes is regulated on the level of cIAP1 and 2. Biochem Biophys Res Commun 290:1308–1314PubMedCrossRef Ruemmele FM, Beaulieu JF, O’Connell J, Bennett MW, Seidman EG, Lentze MJ (2002) The susceptibility to Fas-induced apoptosis in normal enterocytes is regulated on the level of cIAP1 and 2. Biochem Biophys Res Commun 290:1308–1314PubMedCrossRef
31.
go back to reference Seidelin JB (2004) Colonic epithelial cell turnover: possible implications for ulcerative colitis and cancer initiation. Scand J Gastroenterol 39:201–211PubMedCrossRef Seidelin JB (2004) Colonic epithelial cell turnover: possible implications for ulcerative colitis and cancer initiation. Scand J Gastroenterol 39:201–211PubMedCrossRef
32.
go back to reference Seidelin JB, Horn T, Nielsen OH (2003) Simple and efficient method for isolation and cultivation of endoscopically obtained human colonocytes. Am J Physiol Gastrointest Liver Physiol 285:G1122–G1128PubMed Seidelin JB, Horn T, Nielsen OH (2003) Simple and efficient method for isolation and cultivation of endoscopically obtained human colonocytes. Am J Physiol Gastrointest Liver Physiol 285:G1122–G1128PubMed
33.
go back to reference Seidelin JB, Nielsen OH (2006) Expression profiling of apoptosis-related genes in enterocytes isolated from patients with ulcerative colitis. APMIS 114:508–517PubMedCrossRef Seidelin JB, Nielsen OH (2006) Expression profiling of apoptosis-related genes in enterocytes isolated from patients with ulcerative colitis. APMIS 114:508–517PubMedCrossRef
34.
go back to reference Serafini EP, Kirk AP, Chambers TJ (1981) Rate and pattern of epithelial cell proliferation in ulcerative colitis. Gut 22:648–652PubMedCrossRef Serafini EP, Kirk AP, Chambers TJ (1981) Rate and pattern of epithelial cell proliferation in ulcerative colitis. Gut 22:648–652PubMedCrossRef
35.
go back to reference Strater J, Wellisch I, Riedl S, Walczak H, Koretz K, Tandara A, Krammer PH, Moller P (1997) CD95 (APO-1/Fas)-mediated apoptosis in colon epithelial cells: a possible role in ulcerative colitis. Gastroenterology 113:160–167PubMedCrossRef Strater J, Wellisch I, Riedl S, Walczak H, Koretz K, Tandara A, Krammer PH, Moller P (1997) CD95 (APO-1/Fas)-mediated apoptosis in colon epithelial cells: a possible role in ulcerative colitis. Gastroenterology 113:160–167PubMedCrossRef
36.
go back to reference Tadjali M, Seidelin JB, Olsen J, Troelsen JT (2002) Transcriptome changes during intestinal cell differentiation. Biochim Biophys Acta 1589:160–167PubMedCrossRef Tadjali M, Seidelin JB, Olsen J, Troelsen JT (2002) Transcriptome changes during intestinal cell differentiation. Biochim Biophys Acta 1589:160–167PubMedCrossRef
37.
go back to reference Turner DJ, Alaish SM, Zou T, Rao JN, Wang JY, Strauch ED (2007) Bile salts induce resistance to apoptosis through NF-kappaB-mediated XIAP expression. Ann Surg 245:415–425PubMedCrossRef Turner DJ, Alaish SM, Zou T, Rao JN, Wang JY, Strauch ED (2007) Bile salts induce resistance to apoptosis through NF-kappaB-mediated XIAP expression. Ann Surg 245:415–425PubMedCrossRef
38.
go back to reference Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AS Jr (1998) NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281:1680–1683PubMedCrossRef Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AS Jr (1998) NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281:1680–1683PubMedCrossRef
39.
go back to reference Xu X, Fu XY, Plate J, Chong AS (1998) IFN-gamma induces cell growth inhibition by Fas-mediated apoptosis: requirement of STAT1 protein for up-regulation of Fas and FasL expression. Cancer Res 58:2832–2837PubMed Xu X, Fu XY, Plate J, Chong AS (1998) IFN-gamma induces cell growth inhibition by Fas-mediated apoptosis: requirement of STAT1 protein for up-regulation of Fas and FasL expression. Cancer Res 58:2832–2837PubMed
40.
go back to reference Yan SR, Joseph RR, Rosen K, Reginato MJ, Jackson A, Allaire N, Brugge JS, Jobin C, Stadnyk AW (2005) Activation of NF-kappaB following detachment delays apoptosis in intestinal epithelial cells. Oncogene 24:6482–6491PubMed Yan SR, Joseph RR, Rosen K, Reginato MJ, Jackson A, Allaire N, Brugge JS, Jobin C, Stadnyk AW (2005) Activation of NF-kappaB following detachment delays apoptosis in intestinal epithelial cells. Oncogene 24:6482–6491PubMed
Metadata
Title
Upregulation of cIAP2 in regenerating colonocytes in ulcerative colitis
Authors
Jakob B. Seidelin
Ben Vainer
Lars Andresen
Ole H. Nielsen
Publication date
01-12-2007
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 6/2007
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-007-0517-1

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