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Digestive Diseases and Sciences

, Volume 49, Issue 11–12, pp 1738–1744 | Cite as

The Role of Costimulatory Molecules CD80 and CD86 and IFNγ in the Pathogenesis of Ulcerative Colitis

  • Marco Scarpa
  • Roubik Behboo
  • Imerio AngrimanEmail author
  • Barbara Termini
  • Michela Barollo
  • Cesare Ruffolo
  • Lino Polese
  • Renata D’incà
  • Giacomo Carlo Sturniolo
  • Davide Francesco D’amico
Article

Abstract

Several studies showed that costimulatory signals on antigen presenting cells are up-regulated in inflammatory bowel disease. We quantified the expression of CD80, CD86, and IFNγ in colonic mucosa of patients affected by ulcerative colitis and correlated it with clinical and biochemical parameters to identify the context of this up regulation. We enrolled 21 patients affected by ulcerative colitis and 6 healthy subjects. We evaluated for each patient gender, age, duration of disease, clinical, endoscopic and histologic disease activity index, medical therapy, ESR, serum CRP, WBC, and serum αl-acid glycoprotein. CD80, CD86, and IFNγ expression in the colonic mucosa was quantified using reverse transcription polymerase chain reaction. Statistical analysis was performed using Mann–Whitney U test and Spearman’s rank correlation test. Significance was set at P &< 0.05. CD80 was detectable in seven patients, while CD86 and IFNγ expression was evident in all UC patients. CD80 and CD86 were not detectable in control specimens. Colonic CD80 expression was correlated to the age of the patients. CD86 expression showed an inverse correlation with duration of disease and a direct correlation with serum CRP levels and histologic grade of disease activity. IFNγ was not correlated with any of the examined parameter. Our study confirms a major role in ulcerative colitis pathogenesis for CD86 which correlates with histologic grade of disease and with serum CRP levels, and its up-regulation seems to be higher at the beginning of the disease. In “in vivo” conditions IFNγ may not be the only factor responsible for CD86 up-regulation in the ulcerative colitis colonic mucosa.

CD80 CD86 IFNγ ulcerative colitis 

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References

  1. 1.
    Fiocchi C: Inflammatory bowel disease: Aetiology and pathogenesis. Gastroenterology 115:182–205, 1998CrossRefPubMedGoogle Scholar
  2. 2.
    Macpherson A, Khoo UY, Forgacs I, Philpot-Howard J, Bjarson I: Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacterial. Gut 38(3):365–375, 1996CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Duchmann R, Kaiser I, Hermann H: Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease. Clin Exp Immunol 102:448–455, 1995CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Janeway CJ, Bottomly K: Signals and signs for lymphocyte responses. Cell 76:275–285, 1994CrossRefPubMedGoogle Scholar
  5. 5.
    Schwartz RH: A cell culture model for T lymphocyte clonal anergy. Science 248:1349–1356, 1990CrossRefPubMedGoogle Scholar
  6. 6.
    Grewal IS, Flavell RA: A central role of CD40 ligand in the regulation of CD4+ T-cell responses. Immunol Today 17:410–414, 1996CrossRefPubMedGoogle Scholar
  7. 7.
    June CH, Bluestone JA, Nadler LM, Thompson CB: The B7 and CD28 receptor families. Immunol Today 15:321–331, 1994CrossRefPubMedGoogle Scholar
  8. 8.
    Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP: CD28-mediated signalling co-stimulates T cells and prevents induction of anergy in T cell clones. Nature 356:607–609, 1992CrossRefGoogle Scholar
  9. 9.
    Nakazawa A, Watanabe M, Kanai T, et al.: Functional expression of co-stimulatory molecule CD86 on epithelial cells in the inflamed colonic mucosa. Gastroenterology 117(3):726–728, 1999CrossRefGoogle Scholar
  10. 10.
    Li J, Yang Y, Inoue H, Mori M, Akiyoshi T: The expression of costimulatory molecules CD80 and CD86 in human carcinoma cell lines: Its regulation by interferon and interleukin-10, Cancer Immunol Immunother 43:213–219, 1996CrossRefPubMedGoogle Scholar
  11. 11.
    Razi-Wolf Z, Hollander GA, Reiser H: Activation of CD4+ T lymphocytes form IL-2 deficient mice co-stimulatory B7 molecules. Proc Natl Acad Sci USA 93:2903–2908, 1996CrossRefPubMedGoogle Scholar
  12. 12.
    Noguchi M, Hiwatashi N, Liu Z, Toyota T: Enhanced interferon-gamma production and CD86 expression in isolated intestinal mononuclear cells from patients with Crohn’s disease. J Gastroenterology 30 (Suppl 8):52–55, 1995Google Scholar
  13. 13.
    Rugtveit J, Bakka A, Brandtzaeg P: Differential distribution of B7.1 and B7.2 co-stimulatory molecules on mucosal macrophage subsets in human IBD. Clin Exp Immunol 110(1):104–113, 1997CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Rogler G, Hausmann M, Spottl T, Vogl D, Aschenbrenner E, Andus T, Scholmerich J, Gross V: T-cell co—stimulatory molecules are up regulated on intestinal macrophage from inflammatory bowel disease mucosa. Eur J Gastroenterol Hepatol 11:1105–1111, 1999CrossRefPubMedGoogle Scholar
  15. 15.
    Vuckovic S, Florin FHJ, Khalil D, Zhang MF, Patel K, Hamilton I, Hart DNJ: CD40 and CD86 up regulation with divergent CMRF44 expression on blood dendritic cells in inflammatory bowel diseases. Am J Gastroenterol 96(10):2946–2956, 2001CrossRefPubMedGoogle Scholar
  16. 16.
    Polese L, Angriman I, Cecchetto A, Norberto L, Scarpa M, Ruffolo C, Barollo M, Sommariva A, D’Amico DF: The role of CD40 in ulcerative colitis: Histochemical analysis and clinical correlation. Eur J Gastroenterol Hepatol 14:237–241, 2002CrossRefPubMedGoogle Scholar
  17. 17.
    Seo M, Okada M, Yao T, Ueki M, Arima S, Okumura M: An index of disease activity in patients with ulcerative colitis. Am J Gastroenterol 87(8):971–976, 1992PubMedGoogle Scholar
  18. 18.
    Seo M, Okada M, Yao T, et al.: Evaluation of disease activity in patients with moderately active ulcerative colitis: Comparison between a new activity index and Truelove and Witts classification. Am J Gastroenterol 90(10):1759–1763, 1995PubMedGoogle Scholar
  19. 19.
    Baron JH, Connell AM, Lennard-Jones JE: Variation between observers in describing mucosal appearances in proctocolitis. Br Med J 1:89–92, 1964CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Florán C-H, Benoni C, Willán R: Histologic and colonoscopic assessment of disease extension in ulcerative colitis. Scand J Gastroenterol 22:458–462, 1987Google Scholar
  21. 21.
    Stagg AJ, Hart AL, Knight SC, Kamm MA: The dendritic cell: Its role in intestinal inflammation and relationship with gut bacteria. Gut 53:1522–1529, 2003CrossRefGoogle Scholar
  22. 22.
    Pepys MB, Hirschfield GM: C-Reactive protein: A critical update. J Clin Invest 111(12):1805–1812, 2003CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Liskens RK, Van Bodegraven AA, Schoorl M, Tuynman HARE, Bartels P: Predictive value of inflammatory and coagulation parameters in the course of severe ulcerative colitis. Dig Dis Sci 46(3):644–648, 2001CrossRefGoogle Scholar
  24. 24.
    Bitton A, Peppercorn MA, Antonioli DA, Niles JL, Shah S, Bousvaros A, Ransil B, Wild G, Cohen A, Edwardes MD, Stevens AC: Clinical, biologic, and histologic parameters as predictors of relapse in ulcerative colitis. Gastroenterology 120:13–20, 2001CrossRefPubMedGoogle Scholar
  25. 25.
    Mahida YR, Kurlak L, Gallagher A, Hawkey CJ: High circulating levels of IL6 in active Crohn’s disease but noit in ulcerative colitis. Gut 32:1531–1534, 1991CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Nielsen OH, Vainer B, Madsen SM, Seidelin JB, Heegarard NHH: Established and emerging biological activity markers of inflammatory bowel disease. Am J Gastroenterol 95(2):359–367, 2000PubMedGoogle Scholar
  27. 27.
    Kusugami K, Fukatsu A, Tanimoto M, Shinoda M, Harutari k, Kuroiwa A, Ina K, Kanayama K, Ando T, Matsuura T, Yamaguchi T, Morise K, leda M, Iokowa H, Ishiara A, Sarai S: Elevation of IL6 in inflammatory bowel disease is macrophage and epithelial cell dependent. Dig Dis Sci 40:949–959, 1995CrossRefPubMedGoogle Scholar
  28. 28.
    Dijkman R, Bilau A: Interferon-gamma: a key master in immune system. Curr Opin Immunol 1:269–274, 1988CrossRefGoogle Scholar
  29. 29.
    Farrar MA, Schreiber RD: The molecular cell biology of interferon-gamma and its receptor. Annu Rev Immunol 11:571–611, 1993CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2004

Authors and Affiliations

  • Marco Scarpa
    • 1
  • Roubik Behboo
    • 2
  • Imerio Angriman
    • 1
    Email author
  • Barbara Termini
    • 1
  • Michela Barollo
    • 1
  • Cesare Ruffolo
    • 1
  • Lino Polese
    • 1
  • Renata D’incà
    • 3
  • Giacomo Carlo Sturniolo
    • 3
  • Davide Francesco D’amico
    • 1
  1. 1.Dipartimento di Scienze Chirurgiche e Gastroenterologiche, Clinica Chirurgica IUniversity of PadovaPadovaItaly
  2. 2.EndocrinochirurgiaUniversity of PadovaPadovaItaly
  3. 3.GastroenterologiaUniversity of PadovaPadovaItaly

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