Skip to main content
Top
Published in: International Journal of Colorectal Disease 10/2009

01-10-2009 | Original Article

Inflamed pouch mucosa possesses altered tight junctions indicating recurrence of inflammatory bowel disease

Authors: Salah Amasheh, Sonja Dullat, Michael Fromm, Jörg D. Schulzke, Heinz J. Buhr, Anton J. Kroesen

Published in: International Journal of Colorectal Disease | Issue 10/2009

Login to get access

Abstract

Background and aims

The etiology of pouchitis after coloproctomucosectomy with ileal pouch-anal anastomosis in patients with ulcerative colitis is still unknown. Beside changes in luminal antigens, the immunological predisposition is assumed to be responsible. In previous electrophysiological studies, we showed that mucosal barrier and transport function in pouchitis is markedly reduced. Thus, the aim of the present study was to analyze barrier function on the molecular level.

Material and methods

Pouch biopsies of 36 ulcerative colitis patients were analyzed. Time points were (1) intraoperative immediately prior to ileal pouch-anal anastomosis (n = 13), (2) >1 year after ileostomy closure (pouch, n = 12), and (3) during pouchitis (n = 11). Control terminal ileum biopsies were obtained from eight patients undergoing hemicolectomy due to carcinoma. Expression of tight junction proteins was analyzed by Western blotting and confocal laser-scanning microscopy. To elucidate effects on epithelial barrier properties, impedance spectroscopy was performed in miniaturized Ussing chambers.

Results

In pouchitis, epithelial resistance was markedly reduced compared to non-inflamed pouch and control ileum. Expression of tight junction proteins claudin-1, 3, 4, 5, and 7 and occludin revealed differential expression regulation with the tightening tight junction protein claudin-1 being decreased and an increase of the pore-forming claudin-2, whereas other claudins remained constant. Morphometry indicated the mucosal surface to be unchanged.

Conclusion

Pouchitis is characterized by a selective change of tight junction proteins in favor of opening the epithelial tight junction and, thus, the paracellular pathway, which contributes to the inflammatory process. This resembles changes in inflammatory bowel disease (IBD) and indicates IBD recurrence in pouchitis.
Literature
1.
go back to reference Fazio VW, O'Riordain MG, Lavery IC, Church JM, Lau P, Strong SA, Hull T (1998) Long-term functional outcome and quality of life after stapled restorative proctocolectomy. Ann Surg 230:575–584CrossRef Fazio VW, O'Riordain MG, Lavery IC, Church JM, Lau P, Strong SA, Hull T (1998) Long-term functional outcome and quality of life after stapled restorative proctocolectomy. Ann Surg 230:575–584CrossRef
2.
go back to reference Runkel N, Kroesen A, Buhr HJ (1998) Technique and results of ileoanal pouches in ulcerative colitis after colectomy and proctomucosectomy. Zentralbl Chir 123:375–380PubMed Runkel N, Kroesen A, Buhr HJ (1998) Technique and results of ileoanal pouches in ulcerative colitis after colectomy and proctomucosectomy. Zentralbl Chir 123:375–380PubMed
3.
go back to reference Buhr HJ, Heuschen UA, Stern J, Herfarth C (1993) Continence preserving operation after proctocolectomy. Indications, technique and results. Chirurg 64:601–613PubMed Buhr HJ, Heuschen UA, Stern J, Herfarth C (1993) Continence preserving operation after proctocolectomy. Indications, technique and results. Chirurg 64:601–613PubMed
4.
5.
go back to reference Amasheh S, Barmeyer C, Koch CS, Tavalali S, Mankertz J, Epple HJ, Gehring MM, Florian P, Kroesen AJ, Zeitz M, Fromm M, Schulzke JD (2004) Cytokine-dependent transcriptional down-regulation of epithelial sodium channel in ulcerative colitis. Gastroenterology 126:1711–1720PubMedCrossRef Amasheh S, Barmeyer C, Koch CS, Tavalali S, Mankertz J, Epple HJ, Gehring MM, Florian P, Kroesen AJ, Zeitz M, Fromm M, Schulzke JD (2004) Cytokine-dependent transcriptional down-regulation of epithelial sodium channel in ulcerative colitis. Gastroenterology 126:1711–1720PubMedCrossRef
6.
go back to reference Kroesen AJ, Dullat S, Schulzke JD, Fromm M, Buhr H (2008) Permanently increased mucosal permeability in patients with backwash ileitis after ileoanal pouch for ulcerative colitis. Scand J. Gastroenterol. 43:704–711PubMedCrossRef Kroesen AJ, Dullat S, Schulzke JD, Fromm M, Buhr H (2008) Permanently increased mucosal permeability in patients with backwash ileitis after ileoanal pouch for ulcerative colitis. Scand J. Gastroenterol. 43:704–711PubMedCrossRef
7.
go back to reference Kroesen AJ, Leistenschneider P, Lehmann K, Ransco C, Dullat S, Blaut M, Schulzke JD, Fromm M, Buhr HJ (2006) Increased bacterial permeation in long-lasting ileoanal pouches. Inflamm Bowel Dis 12:736–744PubMedCrossRef Kroesen AJ, Leistenschneider P, Lehmann K, Ransco C, Dullat S, Blaut M, Schulzke JD, Fromm M, Buhr HJ (2006) Increased bacterial permeation in long-lasting ileoanal pouches. Inflamm Bowel Dis 12:736–744PubMedCrossRef
8.
go back to reference Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S (1998) Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 141:1539–1550PubMedCrossRef Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S (1998) Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 141:1539–1550PubMedCrossRef
9.
go back to reference Van Itallie C, Rahner C, Anderson JM (2001) Regulated expression of claudin-4 decreases paracellular conductance through a selective decrease in sodium permeability. J Clin Invest 107:1319–1327PubMedCrossRef Van Itallie C, Rahner C, Anderson JM (2001) Regulated expression of claudin-4 decreases paracellular conductance through a selective decrease in sodium permeability. J Clin Invest 107:1319–1327PubMedCrossRef
10.
go back to reference Sawada N, Murata M, Kikuchi K, Osanai M, Tobioka H, Kojima T, Chiba H (2003) Tight junctions and human diseases. Med Electron Microsc 36:147–156PubMedCrossRef Sawada N, Murata M, Kikuchi K, Osanai M, Tobioka H, Kojima T, Chiba H (2003) Tight junctions and human diseases. Med Electron Microsc 36:147–156PubMedCrossRef
11.
go back to reference Furuse M, Hata M, Furuse K, Yoshida Y, Haratake A, Sugitani Y, Noda T, Kubo A, Tsukita S (2002) Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J Cell Biol 56:1099–1111CrossRef Furuse M, Hata M, Furuse K, Yoshida Y, Haratake A, Sugitani Y, Noda T, Kubo A, Tsukita S (2002) Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J Cell Biol 56:1099–1111CrossRef
12.
go back to reference Amasheh S, Schmidt T, Mahn M, Florian P, Mankertz J, Tavalali S, Gitter AH, Schulzke JD, Fromm M (2005) Expression of claudin-5 contributes to barrier properties in tight junctions of epithelial cells. Cell Tissue Res 321:89–96PubMedCrossRef Amasheh S, Schmidt T, Mahn M, Florian P, Mankertz J, Tavalali S, Gitter AH, Schulzke JD, Fromm M (2005) Expression of claudin-5 contributes to barrier properties in tight junctions of epithelial cells. Cell Tissue Res 321:89–96PubMedCrossRef
13.
go back to reference Amasheh S, Meiri N, Gitter AH, Schöneberg T, Mankertz J, Schulzke JD, Fromm M (2002) Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells. J Cell Sci 115:4969–4976PubMedCrossRef Amasheh S, Meiri N, Gitter AH, Schöneberg T, Mankertz J, Schulzke JD, Fromm M (2002) Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells. J Cell Sci 115:4969–4976PubMedCrossRef
14.
go back to reference Bürgel N, Bojarski C, Mankertz J, Zeitz M, Fromm M, Schulzke JD (2002) Mechanisms of diarrhea in collagenous colitis. Gastroenterology 123:433–443PubMedCrossRef Bürgel N, Bojarski C, Mankertz J, Zeitz M, Fromm M, Schulzke JD (2002) Mechanisms of diarrhea in collagenous colitis. Gastroenterology 123:433–443PubMedCrossRef
15.
go back to reference Heller F, Florian P, Bojarski C, Richter J, Christ M, Hillenbrand B, Mankertz J, Gitter AH, Bürgel N, Fromm M, Zeitz M, Fuss I, Strober W, Schulzke JD (2005) Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology 129:550–564PubMed Heller F, Florian P, Bojarski C, Richter J, Christ M, Hillenbrand B, Mankertz J, Gitter AH, Bürgel N, Fromm M, Zeitz M, Fuss I, Strober W, Schulzke JD (2005) Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology 129:550–564PubMed
16.
go back to reference Zeissig S, Bürgel N, Günzel D, Richter J, Mankertz J, Wahnschaffe U, Kroesen AJ, Zeitz M, Fromm M, Schulzke JD (2007) Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Gut 56:61–72PubMedCrossRef Zeissig S, Bürgel N, Günzel D, Richter J, Mankertz J, Wahnschaffe U, Kroesen AJ, Zeitz M, Fromm M, Schulzke JD (2007) Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Gut 56:61–72PubMedCrossRef
17.
go back to reference Sandborn WJ, Tremaine WJ, Batts KP, Pemberton JH, Phillips SF (1994) Pouchitis after ileal pouch-anal anastomosis: a pouchitis disease activity index. Mayo Clin Proc 69:409–415PubMed Sandborn WJ, Tremaine WJ, Batts KP, Pemberton JH, Phillips SF (1994) Pouchitis after ileal pouch-anal anastomosis: a pouchitis disease activity index. Mayo Clin Proc 69:409–415PubMed
18.
go back to reference Stockmann M, Gitter AH, Sorgenfrei D, Fromm M, Schulzke JD (1999) Low edge damage container insert that adjusts intestinal forceps biopsies into Ussing chamber systems. Pflügers Arch 438:107–112PubMedCrossRef Stockmann M, Gitter AH, Sorgenfrei D, Fromm M, Schulzke JD (1999) Low edge damage container insert that adjusts intestinal forceps biopsies into Ussing chamber systems. Pflügers Arch 438:107–112PubMedCrossRef
19.
go back to reference Gitter AH, Schulzke JD, Sorgenfrei D, Fromm M (1997) Ussing chamber for high-frequency transmural impedance analysis of epithelial tissues. J Biochem Biophys Methods 35:81–88PubMedCrossRef Gitter AH, Schulzke JD, Sorgenfrei D, Fromm M (1997) Ussing chamber for high-frequency transmural impedance analysis of epithelial tissues. J Biochem Biophys Methods 35:81–88PubMedCrossRef
20.
go back to reference Schulzke JD, Gitter AH, Mankertz J, Spiegel S, Seidler U, Amasheh S, Saitou M, Tsukita S, Fromm M (2005) Epithelial transport and barrier function in occludin-deficient mice. Biochim Biophys Acta 1669:34–42PubMedCrossRef Schulzke JD, Gitter AH, Mankertz J, Spiegel S, Seidler U, Amasheh S, Saitou M, Tsukita S, Fromm M (2005) Epithelial transport and barrier function in occludin-deficient mice. Biochim Biophys Acta 1669:34–42PubMedCrossRef
21.
go back to reference Kroesen AJ, Stockmann M, Ransco C, Schulzke JD, Fromm M, Buhr HJ (2002) Impairment of epithelial transport but not of barrier function in idiopathic pouchitis after ulcerative colitis. Gut 6:821–826CrossRef Kroesen AJ, Stockmann M, Ransco C, Schulzke JD, Fromm M, Buhr HJ (2002) Impairment of epithelial transport but not of barrier function in idiopathic pouchitis after ulcerative colitis. Gut 6:821–826CrossRef
22.
go back to reference Amasheh S, Milatz S, Krug SM, Bergs M, Amasheh M, Schulzke JD, Fromm M (2009) Na+ absorption defends from paracellular back-leakage by claudin-8 upregulation. Biochem Biophys Res Commun 378:45–50PubMedCrossRef Amasheh S, Milatz S, Krug SM, Bergs M, Amasheh M, Schulzke JD, Fromm M (2009) Na+ absorption defends from paracellular back-leakage by claudin-8 upregulation. Biochem Biophys Res Commun 378:45–50PubMedCrossRef
23.
go back to reference Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S (1993) Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 123:1777–1788PubMedCrossRef Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S (1993) Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 123:1777–1788PubMedCrossRef
24.
go back to reference Ikenouchi J, Furuse M, Furuse K, Sasaki H, Tsukita S, Tsukita S (2005) Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells. J Cell Biol 171:939–945PubMedCrossRef Ikenouchi J, Furuse M, Furuse K, Sasaki H, Tsukita S, Tsukita S (2005) Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells. J Cell Biol 171:939–945PubMedCrossRef
25.
go back to reference Saitou M, Furuse M, Sasaki H, Schulzke JD, Fromm M, Takano H, Noda T, Tsukita S (2000) Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 11:4131–4142PubMed Saitou M, Furuse M, Sasaki H, Schulzke JD, Fromm M, Takano H, Noda T, Tsukita S (2000) Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 11:4131–4142PubMed
26.
go back to reference Reyes JL, Lamas M, Martin D, del Carmen Namorado M, Islas S, Luna J, Tauc M, González-Mariscal L (2002) The renal segmental distribution of claudins changes with development. Kidney Int 62:476–487PubMedCrossRef Reyes JL, Lamas M, Martin D, del Carmen Namorado M, Islas S, Luna J, Tauc M, González-Mariscal L (2002) The renal segmental distribution of claudins changes with development. Kidney Int 62:476–487PubMedCrossRef
27.
go back to reference Dhawan P, Singh AB, Deane NG, No Y, Shiou SR, Schmidt C, Neff J, Washington MK, Beauchamp RD (2005) Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer. J Clin Invest 115:1765–1776PubMedCrossRef Dhawan P, Singh AB, Deane NG, No Y, Shiou SR, Schmidt C, Neff J, Washington MK, Beauchamp RD (2005) Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer. J Clin Invest 115:1765–1776PubMedCrossRef
28.
go back to reference Troeger H, Epple HJ, Schneider T, Wahnschaffe U, Ullrich R, Burchard GD, Jelinek T, Zeitz M, Fromm M, Schulzke JD (2007) Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum. Gut 56:328–335PubMedCrossRef Troeger H, Epple HJ, Schneider T, Wahnschaffe U, Ullrich R, Burchard GD, Jelinek T, Zeitz M, Fromm M, Schulzke JD (2007) Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum. Gut 56:328–335PubMedCrossRef
29.
go back to reference Merrett MN, Soper N, Mortensen N, Jewell DP (1996) Intestinal permeability in the ileal pouch. Gut 39:226–230PubMedCrossRef Merrett MN, Soper N, Mortensen N, Jewell DP (1996) Intestinal permeability in the ileal pouch. Gut 39:226–230PubMedCrossRef
30.
go back to reference Mankertz J, Amasheh M, Krug SM, Fromm A, Amasheh S, Hillenbrand B, Tavalali S, Fromm M, Schulzke JD (2009) TNFalpha up-regulates claudin-2 expression in epithelial HT-29/B6 cells via phosphatidylinositol-3-kinase signaling. Cell Tissue Res 336:67–77PubMedCrossRef Mankertz J, Amasheh M, Krug SM, Fromm A, Amasheh S, Hillenbrand B, Tavalali S, Fromm M, Schulzke JD (2009) TNFalpha up-regulates claudin-2 expression in epithelial HT-29/B6 cells via phosphatidylinositol-3-kinase signaling. Cell Tissue Res 336:67–77PubMedCrossRef
31.
go back to reference Harten SK, Shukla D, Barod R, Hergovich A, Balda MS, Matter K, Esteban MA, Maxwell PH (2009) Regulation of renal epithelial tight junctions by the von Hippel-Lindau tumor suppressor gene involves occludin and claudin 1 and is independent of E-cadherin. Mol Biol Cell 20:1089–1101PubMedCrossRef Harten SK, Shukla D, Barod R, Hergovich A, Balda MS, Matter K, Esteban MA, Maxwell PH (2009) Regulation of renal epithelial tight junctions by the von Hippel-Lindau tumor suppressor gene involves occludin and claudin 1 and is independent of E-cadherin. Mol Biol Cell 20:1089–1101PubMedCrossRef
Metadata
Title
Inflamed pouch mucosa possesses altered tight junctions indicating recurrence of inflammatory bowel disease
Authors
Salah Amasheh
Sonja Dullat
Michael Fromm
Jörg D. Schulzke
Heinz J. Buhr
Anton J. Kroesen
Publication date
01-10-2009
Publisher
Springer-Verlag
Published in
International Journal of Colorectal Disease / Issue 10/2009
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-009-0737-8

Other articles of this Issue 10/2009

International Journal of Colorectal Disease 10/2009 Go to the issue