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Differential expression of pro-inflammatory cytokines and a pro-apoptotic protein in pelvic ileal pouches for ulcerative colitis and familial adenomatous polyposis

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Abstract

Background

Pouchitis after total rectocolectomy is among the most common complications of patients with ulcerative colitis (UC). However, its frequency is quite rare in patients with familial adenomatous polyposis (FAP). We evaluated the inflammatory and pro-apoptotic activity in endoscopically normal mucosa of the ileal pouch in patients with UC and FAP.

Methods

Twenty patients (10 with UC and 10 with FAP) with “J” pouch after total proctocolectomy were studied as were 10 normal controls. Biopsies were obtained from the mucosa of the pouch of UC and FAP patients and from the normal ileum of controls. The expression levels of TNF-α, IL-1β, IL-6, IL-8 and phospho-BAD were determined by immunoblotting. Activated NFκB was evaluated by immuno-precipitation and immunoblotting for IkappaB kinase beta.

Results

Patients with UC had higher levels of IL-1β, IL-6, IL-8 and TNF-α than patients with FAP. The level of TNF-α was higher in patients with UC than in patients with FAP; both patient groups had TNF-α levels higher than controls. Activation of NFκB was similar in all three groups. The expression of phospho-BAD was significantly lower in patients with FAP than in patients with UC.

Conclusions

As compared with patients with FAP, patients with UC presented increased levels of some pro-inflammatory cytokines, even in the absence of clinical or endoscopic signs of pouchitis. Patients with FAP presented lower levels of pro-inflammatory proteins and of phospho-BAD. These findings may explain the higher rates of progression to pouchitis in UC patients, which could correlate with mucosal atrophy that occurs in inflamed tissue.

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References

  1. Parks AG, Nicholls RJ (1978) Proctocolectomy without ileostomy for ulcerative colitis. Br Med J 2:85–87

    Article  CAS  PubMed  Google Scholar 

  2. Utsunomiya J, Iwama T, Imajo M et al (1980) Total colectomy, mucosal proctectomy, and ileoanal anastomosis. Dis Colon Rectum 23:459–466

    Article  CAS  PubMed  Google Scholar 

  3. Nicholls RJ, Moskovitz RL, Shepard NA (1985) Restorative proctocolectomy with ileal reservoir. Br J Surg 72:76–79

    Article  Google Scholar 

  4. Nicholls RJ (1987) Restorative proctocolectomy with various types of reservoir. World J Surg 11:751–762

    Article  CAS  PubMed  Google Scholar 

  5. M’Koma AE (2006) Serum biochemical evaluation of patients with functional pouches ten to 20 years after restorative proctocolectomy. Int J Colorectal Dis 26:1–10

    Google Scholar 

  6. Kiehne K, Brunke G, Wegner F et al (2006) Defensin expression in chronic pouchitis in patients with ulcerative colitis or familial adenomatous polyposis coli. World J Gastroenterol 12:1056–1062

    CAS  PubMed  Google Scholar 

  7. Heuschen UA, Allemeyer EH, Hinz U et al (2002) Diagnosing pouchitis: comparative validation of two scoring system in routine follow-up. Dis Colon Rectum 45:776–786

    Article  PubMed  Google Scholar 

  8. Shen B, Fazio VW, Remzi FH et al (2006) Risk factors for disease of ileal pouch-anal anastomosis after restorative proctocolectomy for ulcerative colitis. Clin Gastroenterol Hepatol 4:81–89

    Article  PubMed  Google Scholar 

  9. Moskowitz RL, Shepard NA, Nicholls RJ (1986) An assessment of inflammation in the reservoir after restorative proctocolectomy with ileoanal ileal reservoir. Int J Colorectal Dis 1:167–174

    Article  CAS  PubMed  Google Scholar 

  10. Armstrong DN, Sillin LF, Chung R (1995) Reduction in tissue blood flow in J-shaped pelvic ileal reservoirs. Dis Colon Rectum 38:526–529

    Article  CAS  PubMed  Google Scholar 

  11. Laake KO, Bjorneklett A, Aamodt G et al (2005) Outcome of four weeks intervention with probiotics on symptoms and endoscopic appearance after surgical reconstruction with a J-configurated ileal-pouch-anal-anastomosis in ulcerative colitis. Scand J Gastroenterol 40:43–51

    Article  CAS  PubMed  Google Scholar 

  12. Ohge H, Furne JK, Springfield J et al (2005) Association between fecal hydrogen sulfide production and pouchitis. Dis Colon Rectum 48:469–475

    Article  PubMed  Google Scholar 

  13. Kuehbacher T, Ott SJ, Helwig U et al (2006) Bacterial and fungal microbiota in relation to probiotic therapy in pouchitis. Gut 55:833–841

    Article  CAS  Google Scholar 

  14. Sandborn WJ (1994) Pouchitis following ileal pouch anal anastomosis: definition, pathogenesis, and treatment. Gastroenterology 107:1856–1860

    CAS  PubMed  Google Scholar 

  15. Nicholls RJ, Banerjee AK (1998) Pouchitis: risk factores, etiology, and treatment. World J Surg 22:347–356

    Article  CAS  PubMed  Google Scholar 

  16. Sandborn WJ, Tremaine WJ, Batts KP et al (1994) Pouchitis after ileal pouch-anal anastomosis: a pouchitis disease activity index. Mayo Clin Proc 69:409–415

    CAS  PubMed  Google Scholar 

  17. Shen B, Achkar JP, Connor JT et al (2003) Modified pouchitis disease activity index. A simplified approach to the diagnosis of pouchitis. Dis Colon Rectum 46:748–753

    Article  PubMed  Google Scholar 

  18. Akerlung JE, Lofberg R (2004) Pouchitis. Curr Opin Gastroenterol 20:341–344

    Article  Google Scholar 

  19. Lohmuller JL, Pemberton JH, Dozois RR et al (1990) Pouchitis and extraintestinal manifestations of inflammatory bowel disease after ileal pouch-anal anastomosis. Ann Surg 211:622–629

    CAS  PubMed  Google Scholar 

  20. Hata K, Watanabe T, Shinozaki M et al (2003) Patients with extraintestinal manifestations have a higher risk of developing pouchitis in ulcerative colitis: multivariate analysis. Scand J Gastroenterol 38:1055–1058

    Article  CAS  PubMed  Google Scholar 

  21. O’shea J, Ma A, Lipsky P (2002) Cytokines and autoimmunity. Nature Rev 2:37–45

    Article  CAS  Google Scholar 

  22. Aggarwal BB (2003) Signalling pathways of the TNF superfamily: a double-edge sword. Nature Rev 3:745–756

    Article  CAS  Google Scholar 

  23. Pullman WE, Elsbury S, Kobayashi M et al (1992) Enhanced mucosal cytokine production in inflammatory bowel disease. Gastroenterology 102:529–537

    CAS  PubMed  Google Scholar 

  24. Raab Y, Gerdin B, Ahlstedt S et al (1993) Neutrophil mucosal involvement is accompanied by enhanced local production of interleukin-8 in ulcerative colitis. Gut 34:1203–1206

    Article  CAS  PubMed  Google Scholar 

  25. Nielsen OH, Brynskov J, Bendizen K (1993) Circulating and mucosal concentrations of tumor necrosis factor and inhibitor(s) in chronic inflammatory bowel disease. Dan Med Bull 40:247–249

    CAS  PubMed  Google Scholar 

  26. Gionchetti P, Campieri M, Belluzzi A et al (1994) Mucosal concentrations of interleukin-1 beta, interleukin-6, interleukin-8, and tumor necrosis factor-alpha in pelvic ileal pouches. Dig Dis Sci 39:1525–1531

    Article  CAS  PubMed  Google Scholar 

  27. Patel RT, Bain I, Youngs D et al (1995) Cytokine production in pouchitis is similar to that in ulcerative colitis. Dis Colon Rectum 38:831–837

    Article  CAS  PubMed  Google Scholar 

  28. Evgenikos N, Bartolo DCC, Hamer-Hodges DW et al (2002) Assessment of ileoanal pouch inflammation by interleukin 1β and interleukin 8 concentrations in the gut lumen. Dis Colon Rectum 45:249–255

    Article  CAS  PubMed  Google Scholar 

  29. Balzano A, Bevilacqua N, Nappo C et al (1998) Cytokines and ulcerative colitis: mucosal balance between pro and anti-inflamatory cytokines in patients with and without pouchitis. Gastroenterology 114:A925

    Article  Google Scholar 

  30. Bulois P, Tremaine WJ, Maunoury V et al (2000) Pouchitis is associated with mucosal imbalance between interleukin-8 and interleukin-10. Inflamm Bowel Dis 6:157–167

    CAS  PubMed  Google Scholar 

  31. Lammers KM, Vergopoulos A, Babel N et al (2005) Probiotic therapy in the prevention of pouchitis onset: decreased interleukin-1β, interleukin-8 and interferon-γ gene expression. Inflamm Bowel Dis 11:447–454

    Article  PubMed  Google Scholar 

  32. Coffey JC, Bennett MW, Wang JH et al (2001) Upregulation of Fas-Fas-L (CD95/CD95L)-mediated epithelial apoptosis-a putative role in pouchitis? J Surg Res 98:27–32

    Article  CAS  PubMed  Google Scholar 

  33. Chen LF, Greene WC (2004) Shaping the nuclear action of NFkB. Nature Rev 5:392–401

    Article  CAS  Google Scholar 

  34. Góes JRN, Fagundes JJ, Coy CSR et al (1994) Preservation of the vascular arcade of the right colon to the mesentery lenghtening in the ileal pouch procedure. Rev Bras Coloproct 14:169–171

    Google Scholar 

  35. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  36. Velloso LA, Folli F, Sun XJ et al (1996) Cross-talk between the insulin and angiotensin signaling systems. Proc Natl Acad Sci USA 93:12490–12495

    Article  CAS  PubMed  Google Scholar 

  37. Araújo EP, De Souza CT, Gasparetti AL et al (2005) Short-term in vivo inhibition of insulin receptor substrate-1 expression leads to insulin resistence, hyperinsulinemia, and increased adiposity. Endocrinology 146:1428–1437

    Article  PubMed  CAS  Google Scholar 

  38. Kuhbacher T, Schreiber S, Runkel N (1998) Pouchitis: pathophysiology and treatment. Int J Colorectal Dis 13:196–207

    Article  CAS  PubMed  Google Scholar 

  39. Tulchinsky H, Hawley PR, Nicholls J (2003) Long-term failure after restorative proctocolectomy for ulcerative colitis. Ann Surg 238:229–234

    PubMed  Google Scholar 

  40. Reinecker HC, Steffen M, Witthoeft T et al (1993) Enhanced secretion of tumor necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patient with ulcerative colitis and Crohn’s disease. Clin Exp Immunol 94:174–181

    CAS  PubMed  Google Scholar 

  41. Wehkamp J, Schwind B, Herrlinger KR et al (2002) Innate immunity and colonic inflammation: enhanced expression of epithelial alpha-defensins. Dig Dis Sci 47:1349–1355

    Article  CAS  PubMed  Google Scholar 

  42. Wehkamp J, Harder J, Weichenthal M et al (2003) Inducible and constitutive beta-defensins are differentially expressed in Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis 9:215–223

    Article  PubMed  Google Scholar 

  43. Sadouk MB, Pelletier JP, Tardif G et al (1995) Human synovial fibroblasts coexpress IL-1 receptor type I and type II mRNA. The increased level of the IL-1 receptor in osteoarthritic cells is related to an increased level of the type I receptor. Lab. Invest 73:347–355

    CAS  PubMed  Google Scholar 

  44. Sandborg CI, Imfeld KL, Zaldivar F Jr et al (1995) IL-4 expression in human T cells is selectively inhibited by IL-1α and IL-1β. J Immunol 155:5206–5212

    CAS  PubMed  Google Scholar 

  45. Colditz I, Zwahlen R, Dewald B et al (1989) In vivo inflammatory activity of neutrophil activating factor, a novel chemotactic peptide derivated from human monocytes. Am J Pathol 134:755–760

    CAS  PubMed  Google Scholar 

  46. Schoeder J, Christophers E (1989) Secretion of novel and homologous neutrophil-activating peptides by LPS-stimulated human endothelial cells. J Immunol 142:244–251

    Google Scholar 

  47. Gross A, McDonnell JM, Korsmeyer SJ (1999) Bcl-2 family members and the mitochondria in apoptosis. Genes Dev 13:1899–1911

    Article  CAS  PubMed  Google Scholar 

  48. Kuwana T, Newmeyer DD (2003) Bcl-2 family proteins and the role of mitochondria in apoptosis. Curr Opin Cell Biol 15:691–699

    Article  CAS  PubMed  Google Scholar 

  49. Vermeulen K, Van Bockstaele DR, Bernemann ZN (2005) Apoptosis: mechanisms and relevance in cancer. Ann Hematol 84:627–639

    Article  CAS  PubMed  Google Scholar 

  50. Widmann C, Gibson S, Johnson GL (1998) Caspase-dependent cleavage of signaling proteins during apoptosis. A turn-off mechanism for anti-apoptotic signals. J Biol Chem 273:7141–7147

    Article  CAS  PubMed  Google Scholar 

  51. Festjens N, Van Gurp M, Van Loo G et al (2004) Bcl-2 family members as sentinels of cellular integrity and role of mitochondrial intermembrane space proteins in apoptotic cell death. Acta Haematol 111:7–27

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine Cellular Signalization Laboratory, Universidade Estadual de Campinas UNICAMP, Campinas, São Paulo, Brazil

    R. F. Leal, C. S. R. Coy, M. L. S. Ayrizono, J. J. Fagundes, M. Milanski, M. J. Saad, L. A. Velloso & J. R. N. Góes

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  1. R. F. Leal
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  2. C. S. R. Coy
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  3. M. L. S. Ayrizono
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  4. J. J. Fagundes
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  5. M. Milanski
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  6. M. J. Saad
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  7. L. A. Velloso
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  8. J. R. N. Góes
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Correspondence to J. R. N. Góes.

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Leal, R.F., Coy, C.S.R., Ayrizono, M.L.S. et al. Differential expression of pro-inflammatory cytokines and a pro-apoptotic protein in pelvic ileal pouches for ulcerative colitis and familial adenomatous polyposis. Tech Coloproctol 12, 33–38 (2008). https://doi.org/10.1007/s10151-008-0395-9

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  • DOI: https://doi.org/10.1007/s10151-008-0395-9

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