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Pattern of Cytokine and Adhesion Molecule mRNA in Hapten-Induced Relapsing Colon Inflammation in the Rat

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Abstract

We examined the mRNA expression of cytokines, chemokines, integrins, and selectins in colon lesions of rat colitis with a semi-quantitative RT-PCR assay. Rat colitis was induced by trinitrobenzene sulfonic acid (TNBS) in 50% ethanol. Within 24 h, an acute inflammation occurred with hyperemia, edema, necrosis and an intense infiltration of granulocytes in the mucosa. The lesion proceeded into a T-lymphocyte/monocyte-driven chronic inflammation for two weeks and healed in 6 weeks. An acute inflammation recurred at the same site when the recovered animals were systemically injected with TNBS. We isolated RNA from colon tissue at 24 h, 1, 2, 4, 6 weeks after TNBS treatment and from the relapsed animals. The mRNA for cytokines IL-1β, IL-6, IL-10 and the chemokines CINC, MIP-1α, MCP-1 were significantly (P < 0.05) elevated and persisted for 2 weeks, decreased in 6 weeks and increased again during relapse. IFNγ mRNA stayed at control levels initially, but increased dramatically in the second weeks of chronic inflammation as well as in relapse. The mRNA levels of adhesion molecules, ICAM-1, VCAM-1, the mucosal homing integrin β7 as well as Pand E-selectin were greatly enhanced between 1 and 3 weeks. The data showed that the chronically inflamed tissue expresses a time-dependent changing pattern of TH1 cytokines and adhesion molecules that maintain the infiltration and activation of inflammatory cells and tissue injury.

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References

  1. MacDermott, R. P. 1994. Alterations in the mucosal immune system in ulcerative colitis and Crohn's disease. Medical Clinics of North America 78:1207–1232.

    Google Scholar 

  2. Dionne, S., J. Hiscott, I. D'Agata, A. Duhaime, and E. G. Seidman. 1997. Quantitative PCR analysis of TNF-α and IL-1β mRNA levels in pediatric IBD mucosal biopsies. Dig. Dis. Sci. 42:1557–1566.

    Google Scholar 

  3. Sartor, R. B. 1997. Pathogenesis and immune mechanisms of chronic inflammatory bowel diseases. Am. J. Grastroenterol. 92:5S–11S.

    Google Scholar 

  4. Strober, W., B. Kelsall, I. J. Fuss, T. Marth, B. Ludviksson, R. Ehrhardt, and M. Neurath. 1997. Reciprocal IFN-γ and TGFβ responses regulate the occurrence of mucosal inflammation. Immunol. Today 18:61–64.

    Google Scholar 

  5. Fukushima, K., G. West, and C. Fiocchi. 1995. Adequacy of mucosal biopsies for evaluation of intestinal cytokine specific mRNA. Dig. Dis. Sci. 40:1498–1505.

    Google Scholar 

  6. Niessner, M., and B. A. Volk. 1995. Altered Th1/Th2 cytokine profiles in the intestinal mucosa of patients with inflammatory bowel disease as assessed by quantitative reversed transcribed polymerase chain reaction (RT-PCR). Clin. Exp. Immunol. 101:428–435.

    Google Scholar 

  7. Fuss, I. J., M. Neurath, M. Boirivant, J. S. Klein, C. De La Motte, S. A. Strong, C. Fiocchi, and W. Strober. 1996. Disparate CD4+ lamina propria lymphokine secretion profiles in inflammatory bowel disease. J. Immunol. 157:1261–1270.

    Google Scholar 

  8. Wong, P. Y. K., G. Yue, K. Yin, M. Miyasaka, C. L. Lane, A. M. Manning, D. C. Anderson, and F. F. Sun. 1995. Antibodies to ICAM-1 ameliorate the inflammatory response in acetic acid induced inflammatory bowel disease. J. Pharmacol. Exptl. Therap. 274:475–480.

    Google Scholar 

  9. Elson, C. O., R. B. Sartor, G. S. Tennyson, and R. H. Riddell. 1995. Experimental models of inflammatory bowel disease. Gastroenterol. 109:1344–1367.

    Google Scholar 

  10. Morrissey, P. J., K. Charrier, S. Braddy, D. Liggitt, and R. L. Coffman. 1993. CD4+ T cells that express high levels of CD45RB induce wasting disease when transferred into congenic severe combined immunodeficient mice: disease development is prevented by cotransfer of purified CD4+ T cells. J. Exp. Med. 178:237–241.

    Google Scholar 

  11. Yue, G., F. F. Sun, C. J. Dunn, K. Yin, and P. Y.-K. Wong. 1996. The 21-aminosteroid tirilazad mesylate ameliorate inflammatory bowel disease (IBD) in rats. J. Pharm. Exptl. Therap. 276:265–269.

    Google Scholar 

  12. Appleyard, C. B., and J. L. Wallace. 1995. Reactivation of hapteninduced colitis and its prevention by anti-inflammatory drugs. Amer. J. Physiol. 269:G119–G125.

    Google Scholar 

  13. Bradley, P. P., D. A. Priebat, R. D. Christensen, and G. Rothstein. 1982. Measurement of cutaneous inflammation: Estimation of neutrophil content with an enzyme marker. J. Invest Dermatol. 78:206–209.

    Google Scholar 

  14. Krzesicki, R. F., G. E. Winterrowd, J. R. Brashler, C. A. Hat-field, R. L. Griffin, S. F. Fidler, K. P. Kolbasa, K. L. Shull, I. M. Richards, and J. E. Chin. 1997. Identification of cytokine and adhesion molecule mRNA in murine lung tissue and isolated T cells and eosinophils by semi-quantitative reverse transcriptase-polymerase chain reaction. Am. J. Respir. Cell Mol. Biol. 16:693–701.

    Google Scholar 

  15. Dieleman, L. A., C. O. Elson, G. S. Tennyson, and K. W. Beagley. 1996. Kinetics of cytokine expression during healing of acute colitis in mice. Amer. J. Physiol. 271:G130–G136.

    Google Scholar 

  16. Neurath, M. F., I. J., Fuss, M. Pasparakis, L. Alexopouloum, L. Haralambous, K. H. Meyer Zum Buschenfelde, W. Strober, and G. Kollias. 1997. Predominant pathogenic role of tumor necrosis factor in experimental colitis in mice. Europ. J. Immunol. 27:1743–1750.

    Google Scholar 

  17. Andus, T., R. Daig, D. Vogl, E. Aschenbrenner, G. Lock, S. Hollerbach, M. Kollinger, J. Scholmerich, and V. Gross. 1997. Imbalance of the interleukin 1 system in colonic mucosa-association with intestinal inflammation and interleukin 1 receptor agonist genotype 2, Gut 41:651–657.

    Google Scholar 

  18. Nielsen, O. H., N. Rudiger, M. Gaustadnes, and T. Horn. 1997. Intestinal interleukin-8 concentration and gene expression in inflammatory bowel disease. Scand. J. Gastroenterology 32:1028–1034.

    Google Scholar 

  19. Reinecker, H. C., E. Y. Loh, D. J. Ringler, A. Mehta, J. L. Rombeau, and R. P. MacDermott. 1995. Monocyte-chemoattractant protein 1 gene expression in intestinal epithelial cells and inflammatory bowel disease mucosa. Gastroenterol. 108:40–50.

    Google Scholar 

  20. Neurath, M. F., I. J. Fuss, B. L. Kelsall, E. Stuber, and W. Strober. 1995. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J. Exptl. Med. 182:1281–1290.

    Google Scholar 

  21. Noguchi, M., N. Hiwatashi, Z. Liu, and T. Toyota. 1995. Enhanced interferon-g production and B7-2 expression in isolated intestinal mononuclear cells from patients with Crohn's disease. J. Gastroenterol. 30 Suppl 8, 52–55.

    Google Scholar 

  22. Monteleone, G., L. Biancone, R. Marasco, G. Morrone, O. Marasco, F. Luzza, and F. Pallone. 1997. Interleukin 12 is expressed and actively released by Crohn's disease intestinal lamina propria mononuclear cells. Gastroenterol. 112:1169–1178.

    Google Scholar 

  23. Babyatsky, M. W., G. Rossiter, and D. K. Podolsky. 1996. Expression of transforming growth factors a and b in colonic mucosa in inflammatory bowel disease. Gastroenterol. 110:975–984.

    Google Scholar 

  24. Adjei, A. A., C. K. Ameho, E. K. Harrison, K. Yamauchi, A. Kulkarni, A. Kawajiri, and S. Yamamoto. 1997. Nucleosidenucleotide-free diet suppresses cytokine production and contact sensitivity responses in rats with trinitrobenzene sulphonic acidinduced colitis. Amer. J. Med. Sci. 314:89–96.

    Google Scholar 

  25. Hogaboam, C. M., B. A. Vallance, A. Kumar, C. L. Addison, F. L. Graham, J. Gauldie, and S. M. Collins. 1997. Therapeutic effects of interleukin-4 gene transfer in experimental inflammatory bowel disease. J. Clin. Invest. 100:2766–2776.

    Google Scholar 

  26. Nakamura, S., H. Ohtani, Y. Watanabe, K. Fukushima, T. Matsumoto, A. Kitano, K. Kobayashi, and H. Nagura. 1993. In situ Expression of the cell adhesion molecules in inflammatory bowel disease. Lab. Invest. 69:77–85.

    Google Scholar 

  27. Schurmann, G. M., A. E. Bishop, P. Facer, M. Vecchio, J. C. Lee, D. S. Rampton, and J. M. Polak. 1995. Increased expression of cell adhesion molecule P-selectin in active inflammatory bowel disease. Gut 36:411–418.

    Google Scholar 

  28. Briskin, M. J., D. Winsor-Hines, A. Shyjan, N. Cochran, S. Bloom, J. Wilson, L. M. McEvoy, E. C. Butcher, N. Kassam, C. R. MacKay, W. Newman, and D. J. Ringler. 1997. Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. Amer. J. Pathol. 151:97–110.

    Google Scholar 

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Sun, F.F., Lai, PS., Yue, G. et al. Pattern of Cytokine and Adhesion Molecule mRNA in Hapten-Induced Relapsing Colon Inflammation in the Rat. Inflammation 25, 33–45 (2001). https://doi.org/10.1023/A:1007023611478

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