2014 | 4 | 1 | 75-82
Article title

The expression of apoptosis-related proteins in patients with ulcerative colitis

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Purpose: Recent literature data indicate a key role of apoptosis in the pathogenesis of inflammatory bowel disease. The aim of the study was to evaluate the expression of Bax, Bid, Bcl-2 and Bcl-xl in non-dysplastic and dysplastic epithelium in inflamated mucosa of patients with ulcerative colitis. Methods: The study consists of 18 patients with diagnosed ulcerative colitis. The expression of proteins was determined immunohistochemically. Results: Lack of Bax expression in normal epithelium of the inflamed intestinal mucosa (94.4%) and a weak expression of this protein were found in dysplastic glandular cells (67%). The Bax expression of dysplastic epithelium correlates with reduced severity of chronic inflammation (p<0.005). Bid expression in non-dysplastic glands was found in 67% of cases vs. 16% in dysplastic epithelium that was associated with the occurrence of epithelial erosions or ulcers (p<0.05). Moderate cytoplasmic expression of Bcl-xl was noted in 27.7% of patients in normal epithelium and in 66.1% within dysplastic lesions. Bcl-xl expression in dysplastic glandular cells correlated with the presence of neutrophils in the lamina propria (p <0.05). Conclusions: The immunohistochemical expressions of Bax, Bcl-2 and Bcl-xl increase and Bid protein expression decreases in dysplastic glandular tubes as compared to non-dysplastic intestinal epithelium in inflamed mucosa, which may suggest an imbalance of controlled cell death in ulcerative colitis.
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  • Iwamoto M, Koji T, Makiyama K, Kobayashi N, Nakane PK. Apoptosis of crypt epithelial cells in ulcerative colitis. J Pathol. 1996 Oct;180(2):152-9.
  • Zawadzka P. Nieswoiste zapalenia jelit- wczoraj i dziś. Now Lek. 2006: 5: 480-5.
  • Chichlowski M, Hale LP. Bacterial-mucosal interactions in inflammatory bowel disease: an alliance gone bad. Am J Physiol Gastrointest Liver Physiol. 2008 Dec; 295(6):G1139-49.
  • Mankertz J, Schulzke JD. Altered permeability in inflammatory bowel disease: patho-physiology and clinical implications. Curr Opin Gastroenterol. Curr Opin Gastroenterol. 2007 Jul;23(4):379-83.
  • Rupniewska Z, Bojarska-Junak A. Apoptoza: przepuszczalność błony mitochondrialnej i rola pełniona przez białka z rodziny Bcl-2. Postepy Hig Med Dosw (Online). 2004;58:538-47.
  • Korsmeyer SJ. Bcl-2 initiates a new category of oncogenes regulators of cell death. Blood. 1992 Aug 15;80(4):879-86.
  • Schmitz H, Barmeyer C, Fromm M, Runkel N, Foss HD, Bentzel CJ, Riecken EO, Schulzke JD. Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis. Gastroenterology. 1999 Feb;116(2):301-9.
  • Wong MH, Huelsken J, Birchmeier W, Gordon JI. Selection of multipotent stem cells during morphogenesis of small intestinal crypts of Lieberkuhn is perturbed by stimulation of Lef-1/beta-catenin signaling. J Biol Chem. 2002 May 3;277(18):15843-50.
  • Edelblum KL, Yan F, Yamaoka T, Polk DB. Regulation of apoptosis during homeostasis and disease in the intestinal epithelium. Inflamm Bowel Dis. 2006 May;12(5):413-24.
  • Geboes K, Riddell R, Ost A, Jensfelt B, Persson T, Löfberg R. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut. 2000 Sep;47(3):404-9.
  • Giriş M, Depboylu B, Doğru-Abbasoğlu S, Erbil Y, Olgaç V, Aliş H, Aykaç-Toker G, Uysal M. Effect of taurine on oxidative stress and apoptosis-related protein expression in trinitrobenzene sulphonic acid-induced colitis. Clin Exp Immunol. 2008 Apr;152(1):102-10.
  • Ciccocioppo R, Di Sabatino A, Gasbarrini G, Corazza GR. Apoptosis and gastrointestinal tract. Ital J Gastroenterol Hepatol. 1999 Mar;31(2):162-72.
  • Iimura M, Nakamura T, Shinozaki S, Iizuka B, Inoue Y, Suzuki S, Hayashi N. Bax is downregulated in inflamed colonie mucoas of ulcerative colitis. Gut. 2000 Aug;47(2):228-35.
  • Karamanolis DG, Kyrlagkitsis I, Konstantinou K, Papatheodoridis GV, Karameris A, Mallas E, Ladas SD, Raptis S. The Bcl-2/Bax system and apoptosis in ulcerative colitis. Hepato-gastroenterology. 2007 Jun;54(76):1085-8.
  • Kouklakis G, Kountouras J, Molyvas E. Oncogenes’s expression in bowel tissue samples of patients with inflammatory bowel disease: A pilot study. Hepatogastroenterology 2001; 48(Suppl I): XXXIX.
  • Leal RF, Ayrizono Mde L, Milanski M, Fagundes JJ, Moraes JC, Meirelles LR, Velloso LA, Coy CS. Detection of epithelial apoptosis in pelvic ileal pouches for ulcerative colitis and familial adenomatous polyposis. J Transl Med. 2010 Jan 29;8:11.
  • Yoshida T, Matsumoto N, Mikami T, Okayasu I. Upregulation of p16(INK4A) and Bax in p53 wild/p53-overexpressing crypts in ulcerative colitis-associated tumors. Br J Cancer. 2004 Sep 13; 91 (6):1081-8.
  • Seidelin JB, Nielsen OH. Epithelial apoptosis: cause or consequence of ulcerative colitis? Scand J Gastroenterol. 2009;44(12):1429-34.
  • Van der Woude CJ, Moshage H, Homan M, Kleibeuker JH, Jansen PL, van Dekken H. Expression of apoptosis related proteins during malignant progression in chronic ulcerative colitis. J Clin Pathol. 2005 Aug;58(8):811-4.
  • Brüwer M, Schmid KW, Senninger N, Schürmann G. Immunohistochemical expre-ssion of P53 and oncogenes in ulcerative colitis-associated colorectal carcinoma. World J Surg. 2002 Mar; 26(3):390-6.
  • Mikami T, Yoshida T, Akino F, Motoori T, Yajima M, Okayasu I. Apoptosis regulation differs between ulcerative colitis-associated and sporadic colonic tumors. Association with survivin and bcl-2. Am J Clin Pathol. 2003 May;119(5):723-30.
  • Ina K, Itoh J, Fukushima K, Kusugami K, Yamaguchi T, Kyokane K, Imada A, Binion DG, Musso A, West GA, Dobrea GM, McCormick TS, Lapetina EG, Levine AD, Ottaway CA, Fiocchi C.Resistance of Crohn's disease T cells to multiple apoptotic signals is associated with a Bcl-2/Bax mucosal imbalance. J Immunol. 1999 Jul 15;163(2):1081-90.
  • Itoh J, de La Motte C, Strong SA, Levine AD, Fiocchi C.Decreased Bax expression by mucosal T cells favours resistance to apoptosis in Crohn’s disease. Gut. 2001 Jul; 49(1):35-41.
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