Abstract
Background and aims
The chemokine MCP-1 is thought to be important for the recruitment of mononuclear cells and the maintenance of inflammation in inflammatory bowel disease. We investigated whether MCP-1 protein expression is correlated with the degree of mucosal inflammation in patients with Crohn's disease. Furthermore, we studied whether a functional single nucleotide polymorphism (G or A) located in the distal regulatory region of the MCP-1 gene is associated with Crohn's disease and/or its phenotype.
Patients and methods
MCP-1 concentration in tissue homogenates was analyzed in mucosal biopsy specimens of 31 patients with Crohn's disease and 48 controls by enzyme-linked immunosorbent assay, and the correlation with an endoscopic macroscopic score was analyzed. In 179 patients with Crohn's disease and 189 controls MCP-1 genotyping was carried out by polymerase chain reaction restriction fragment length polymorphism technique. Subgroup phenotypic analysis was performed according to the Vienna classification.
Results
MCP-1 tissue concentrations were significantly associated with the macroscopic degree of inflammation. The gene frequency of the different MCP-1 alleles did not differ from healthy controls. However, the G/A and G/G genotype was significantly decreased in patients with a later onset of the disease and both genotypes presented also less frequently with a fistulizing disease behavior.
Conclusion
The degree of intestinal inflammation in Crohn's disease is associated with MCP-1 tissue levels. Furthermore there is evidence for an association of different disease behavior with different MCP-1 genotypes.
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References
Fiocchi C (1998) Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 115:182–205
Hugot JP, Zouali H, Lesage S, Thomas G (1999) Etiology of the inflammatory bowel diseases. Int J Colorectal Dis 14:2–9
Mackay CR (2001) Chemokines: immunology's high impact factors. Nat Immunol 2:95–101
Luster AD (1998) Chemokines-chemotactic cytokines that mediate inflammation. N Engl J Med 338:436–445
Gu L, Tseng SC, Rollins BJ (1999) Monocyte chemoattractant protein-1. Chem Immunol 72:7–29
Mazzucchelli L, Hauser C, Zgraggen K, Wagner HE, Hess MW, Laissue JA, Mueller C (1996) Differential in situ expression of the genes encoding the chemokines MCP-1 and RANTES in human inflammatory bowel disease. J Pathol 178:201–206
Reinecker HC, Loh EY, Ringler DJ, Mehta A, Rombeau JL, MacDermott RP (1995) Monocyte-chemoattractant protein 1 gene expression in intestinal epithelial cells and inflammatory bowel disease mucosa. Gastroenterology 108:40–50
Grimm MC, Elsbury SK, Pavli P, Doe WF (1996) Enhanced expression and production of monocyte chemoattractant protein-1 in inflammatory bowel disease mucosa. J Leukoc Biol 59:804–812
Uguccioni M, Gionchetti P, Robbiani DF, Rizzello F, Peruzzo S, Campieri M, Baggiolini M (1999) Increased expression of IP-10, IL-8, MCP-1, and MCP-3 in ulcerative colitis. Am J Pathol 155:331–336
Jung HC, Eckmann L, Yang SK, Panja A, Fierer J, Morzycka-Wroblewska E, Kagnoff MF (1995) A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J Clin Invest 95:55–65
Rovin BH, Lu L, Saxena R (1999) A novel polymorphism in the MCP-gene regulatory region that influences MCP-1 expression. Biochem Biophys Res Commun 259:344–348
Jibiki T, Terai M, Shima M, Ogawa A, Hamada H, Kanazawa M, Yamamoto S, Oana S, Kohno Y (2001) Monocyte chemoattractant protein 1 gene regulatory region polymorphism and serum levels of monocyte chemoattractant protein 1 in Japanese patients with Kawasaki disease. Arthritis Rheum 44:2211–2212
Szalai C, Kozma GT, Nagy A, Bojszko A, Krikovszky D, Szabo T, Falus A (2001) Polymorphism in the gene regulatory region of MCP-1 is associated with asthma susceptibility and severity. J Allergy Clin Immunol 108:375–381
Szalai C, Duba J, Prohaszka Z, Kalina A, Szabo T, Nagy B, Horvath L, Csaszar A (2001) Involvement of polymorphisms in the chemokine system in the susceptibility for coronary artery disease (CAD). Coincidence of elevated Lp (a) and MCP-1-2518 G/G genotype in CAD patients. Atherosclerosis 158:233–239
Mahida YR, Wu K, Jewell DP (1989) Enhanced production of interleukin 1-beta by mononuclear cells isolated from mucosa with active ulcerative colitis of Crohn's disease. Gut 30:835–838
Youngman KR, Simon PL, West GA, Cominelli F, Rachmilewitz D, Klein JS, Fiocchi C (1993) Localization of intestinal interleukin 1 activity and protein and gene expression to lamina propria cells. Gastroenterology 104:749–758
Gasche C, Scholmerich J, Brynskov J, D'Haens G, Hanauer SB, Irvine EJ, Jewell DP, Rachmilewitz D, Sachar DB, Sandborn WJ, Sutherland LR (2000) A simple classification of Crohn's disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998. Inflamm Bowel Dis 6:8–15
Lashner BA (2000) Clinical features, laboratory findings and course of Crohn's disease. In: Kirshner JB (ed) Inflammatory bowel disease. Saunders, Philadelphia, pp 305–314
Daig R, Andus T, Aschenbrenner E, Falk W, Schölmerich J, Gross V (1996) Increased interleukin 8 expression in the colon mucosa of patients with inflammatory bowel disease. Gut 38:216–222
Rogler G, Brand K, Vogel D, Page S, Hofmeister R, Andus T, Knuechel R, Baeuerle PA, Schölmerich J, Gross V (1998) Nuclear factor-kappa B is activated in macrophages and epithelial cells of inflamed intestinal mucosa. Gastroenterology 115:357–369
Holm S (1979) A simple sequentially rejective multiple test procedure. Scand J Stat 6:1161–1168
Papadakis KA, Targan SR (2000) The role of chemokines and chemokine receptors in mucosal inflammation. Inflamm Bowel Dis 6:303–313
Petronis A, Petroniene R (2000) Epigenetics of inflammatory bowel disease. Gut 47:302–306
Karpus WJ, Lukacs NW, Kennedy KJ, Smith WS, Hurst SD, Barrett TA (1997) Differential CC chemokine-induced enhancement of T helper cell cytokine production. J Immunol 158:4129–4136
Gu L, Tseng S, Horner RM, Tam C, Loda M, Rollins BJ (2000) Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature 404:407–411
Chensue SW, Warmington KS, Ruth JH, Sanghi PS, Lincoln P, Kunkel SL (1996) Role of monocyte chemoattractant protein-1 (MCP-1) in Th1 (mycobacterial) and Th2 (schistosomal) antigen-induced granuloma formation: relationship to local inflammation, Th cell expression, and IL-12 production. J Immunol 157:4602–4608
Matsukawa A, Lukacs NW, Standiford TJ, Chensue SW, Kunkel SL (2000) Adenoviral-mediated overexpression of monocyte chemoattractant protein-1 differentially alters the development of Th1 and Th2 type responses in vivo. J Immunol 164:1699–1704
Karpus WJ, Kennedy KJ, Kunkel SL, Lukacs NW (1998) Monocyte chemotactic protein 1 regulates oral tolerance induction by inhibition of T helper cell 1-related cytokines. J Exp Med 187:733–741
Louis E, Collard A, Oger AF, Degroote E, Aboul Nasr El Yafi FA, Belaiche J (2001) Behaviour of Crohn's disease according to the Vienna classification: changing pattern over the course of the disease. Gut 49:777–782
Acknowledgements
This work was supported by the Kompetenznetzwerk Chronisch entzündliche Darmerkrankungen of the Ministry for Education and Research (BMBF).
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Herfarth, H., Göke, M., Hellerbrand, C. et al. Polymorphism of monocyte chemoattractant protein 1 in Crohn's disease. Int J Colorectal Dis 18, 401–405 (2003). https://doi.org/10.1007/s00384-003-0477-0
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DOI: https://doi.org/10.1007/s00384-003-0477-0