Gastroenterology
Volume 132, Issue 1 , Pages 166-175 , January 2007

A Functional Role for Interleukin-21 in Promoting the Synthesis of the T-Cell Chemoattractant, MIP-3α, by Gut Epithelial Cells

  • Roberta Caruso

      Affiliations

    • Dipartimento di Medicina Interna e Centro di Eccellenza per lo Studio delle Malattie Complesse e Multifattoriali, Università Tor Vergata, Rome, Italy
    • R.C. and D.F. contributed equally to this study.
    • ,
  • Daniele Fina

      Affiliations

    • Dipartimento di Medicina Interna e Centro di Eccellenza per lo Studio delle Malattie Complesse e Multifattoriali, Università Tor Vergata, Rome, Italy
    • R.C. and D.F. contributed equally to this study.
    • ,
  • Ilaria Peluso

      Affiliations

    • Dipartimento di Medicina Interna e Centro di Eccellenza per lo Studio delle Malattie Complesse e Multifattoriali, Università Tor Vergata, Rome, Italy
    • ,
  • Carmine Stolfi

      Affiliations

    • Dipartimento di Medicina Interna e Centro di Eccellenza per lo Studio delle Malattie Complesse e Multifattoriali, Università Tor Vergata, Rome, Italy
    • ,
  • Massimo Claudio Fantini

      Affiliations

    • Dipartimento di Medicina Interna e Centro di Eccellenza per lo Studio delle Malattie Complesse e Multifattoriali, Università Tor Vergata, Rome, Italy
    • ,
  • Valentina Gioia

      Affiliations

    • Dipartimento di Medicina Interna e Centro di Eccellenza per lo Studio delle Malattie Complesse e Multifattoriali, Università Tor Vergata, Rome, Italy
    • ,
  • Flavio Caprioli

      Affiliations

    • Dipartimento di Medicina Interna e Centro di Eccellenza per lo Studio delle Malattie Complesse e Multifattoriali, Università Tor Vergata, Rome, Italy
    • ,
  • Giovanna Del Vecchio Blanco

      Affiliations

    • Dipartimento di Medicina Interna e Centro di Eccellenza per lo Studio delle Malattie Complesse e Multifattoriali, Università Tor Vergata, Rome, Italy
    • ,
  • Omero Alessandro Paoluzi

      Affiliations

    • Dipartimento di Medicina Interna e Centro di Eccellenza per lo Studio delle Malattie Complesse e Multifattoriali, Università Tor Vergata, Rome, Italy
    • ,
  • Thomas T. MacDonald

      Affiliations

    • Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, London, United Kingdom
    • ,
  • Francesco Pallone

      Affiliations

    • Dipartimento di Medicina Interna e Centro di Eccellenza per lo Studio delle Malattie Complesse e Multifattoriali, Università Tor Vergata, Rome, Italy
    • ,
  • Giovanni Monteleone

      Affiliations

    • Dipartimento di Medicina Interna e Centro di Eccellenza per lo Studio delle Malattie Complesse e Multifattoriali, Università Tor Vergata, Rome, Italy
    • Corresponding Author InformationAddress requests for reprints to: Giovanni Monteleone, MD, Dipartimento di Medicina Interna, Università Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy. fax: (39) 06-72596391.

Received 28 June 2006 ,Accepted 14 September 2006.

References 

  1. Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis. 2006;12(Suppl 1):S3–S9
  2. Papadakis KA. Chemokines in inflammatory bowel disease. Curr Allergy Asthma Rep. 2004;4:83–89
  3. Leonard WJ, Spolski R. Interleukin-21: a modulator of lymphoid proliferation, apoptosis and differentiation. Nat Rev Immunol. 2005;5:688–698
  4. Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA, et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature. 2000;408:57–63
  5. Monteleone G, Monteleone I, Fina D, Vavassori P, Del Vecchio Blanco G, Caruso R, et al. Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn’s disease. Gastroenterology. 2005;128:687–694
  6. Jungel A, Distler JH, Kurowska-Stolarska M, Seemayer CA, Seibl R, Forster A, et al. Expression of interleukin-21 receptor, but not interleukin-21, in synovial fibroblasts and synovial macrophages of patients with rheumatoid arthritis. Arthritis Rheum. 2004;50:1468–1476
  7. Distler JH, Jungel A, Kowal-Bielecka O, Michel BA, Gay RE, Sprott H, et al. Expression of interleukin-21 receptor in epidermis from patients with systemic sclerosis. Arthritis Rheum. 2005;52:856–864
  8. Kucharzik T, Hudson JT, Lugering A, Abbas JA, Bettini M, Lake JG, et al. Acute induction of human IL-8 production by intestinal epithelium triggers neutrophil infiltration without mucosal injury. Gut. 2005;54:1565–1572
  9. Kim JA, Kim DK, Kang OH, Choi YA, Park HJ, Choi SC, et al. Inhibitory effect of luteolin on TNF-alpha-induced IL-8 production in human colon epithelial cells. Int Immunopharmacol. 2005;5:209–217
  10. Schwartz S, Beaulieu JF, Ruemmele FM. Interleukin-17 is a potent immuno-modulator and regulator of normal human intestinal epithelial cell growth. Biochem Biophys Res Commun. 2005;337:505–509
  11. Fyfe M, Bergstrom M, Aspengren S, Peterson A. PAR-2 activation in intestinal epithelial cells potentiates interleukin-1beta-induced chemokine secretion via MAP kinase signaling pathways. Cytokine. 2005;31:358–367
  12. Reibman J, Hsu Y, Chen LC, Bleck B, Gordon T. Airway epithelial cells release MIP-3alpha/CCL20 in response to cytokines and ambient particulate matter. Am J Respir Cell Mol Biol. 2003;28:648–654
  13. Scapini P, Crepaldi L, Pinardi C, Calzetti F, Cassatella MA. CCL20/macrophage inflammatory protein-3alpha production in LPS-stimulated neutrophils is enhanced by the chemoattractant formyl-methionyl-leucyl-phenylalanine and IFN-gamma through independent mechanisms. Eur J Immunol. 2002;32:3515–3524
  14. Brenne AT, Ro TB, Waage A, Sundan A, Borset M, Hjorth-Hansen H. Interleukin-21 is a growth and survival factor for human myeloma cells. Blood. 2002;99:3756–3762
  15. Pelletier M, Bouchard A, Girard D. In vivo and in vitro roles of IL-21 in inflammation. J Immunol. 2004;173:7521–7530
  16. Teramoto K, Miura S, Tsuzuki Y, Hokari R, Watanabe C, Inamura T, et al. Increased lymphocyte trafficking to colonic microvessels is dependent on MAdCAM-1 and C-C chemokine mLARC/CCL20 in DSS-induced mice colitis. Clin Exp Immunol. 2005;139:421–428
  17. Varona R, Villares R, Carramolino L, Goya I, Zaballos A, Gutierrez J, et al. CCR6-deficient mice have impaired leukocyte homeostasis and altered contact hypersensitivity and delayed-type-hypersensitivity responses. J Clin Invest. 2001;107:37–45
  18. Yu Y, Sitaraman S, Gewirtz AT. Intestinal epithelial cell regulation of mucosal inflammation. Immunol Res. 2004;29:55–68
  19. Pizarro TT, Michie MH, Bentz M, Woraratanadharm J, Smith MF, Foley E, et al. IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn’s disease: expression and localization in intestinal mucosal cells. J Immunol. 1999;162:6829–6835
  20. Mizoguchi E, Mizoguchi A, Takedatsu H, Cario E, de Jong YP, Ooi CJ, et al. Role of tumor necrosis factor receptor 2 (TNFR2) in colonic epithelial hyperplasia and chronic intestinal inflammation in mice. Gastroenterology. 2002;122:134–144
  21. Schutyser E, Struyf S, Van Damme J. The CC chemokine CCL20 and its receptor CCR6. Cytokine Growth Factor Rev. 2003;14:409–426
  22. Rhee SH, Keates AC, Moyer MP, Pothoulakis C. MEK is a key modulator for TLR5-induced interleukin-8 and MIP3alpha gene expression in non-transformed human colonic epithelial cells. J Biol Chem. 2004;279:25179–25188
  23. Kao CY, Huang F, Chen Y, Thai P, Wachi S, Kim C, et al. Up-regulation of CC chemokine ligand 20 expression in human airway epithelium by IL-17 through a JAK-independent but MEK/NF-kappaB-dependent signaling pathway. J Immunol. 2005;175:6676–6685
  24. Kwon JH, Keates S, Bassani L, Mayer LF, Keates AC. Colonic epithelial cells are a major site of macrophage inflammatory protein 3alpha (MIP-3alpha) production in normal colon and inflammatory bowel disease. Gut. 2002;51:818–826
  25. Kaser A, Ludwiczek O, Holzmann S, Moschen AR, Weiss G, Enrich B, et al. Increased expression of CCL20 in human inflammatory bowel disease. J Clin Immunol. 2004;24:74–85
  26. Vollmer TL, Liu R, Price M, Rhodes S, La Cava A, Shi FD. Differential effects of IL-21 during initiation and progression of autoimmunity against neuroantigen. J Immunol. 2005;174:2696–2701

 Supported by the “Fondazione Umberto di Mario,” Rome, the Broad Medical Research Program Foundation (grant no. IBD-0154R), and Giuliani SpA, Milan, Italy.

PII: S0016-5085(06)02221-9

doi: 10.1053/j.gastro.2006.09.053

Gastroenterology
Volume 132, Issue 1 , Pages 166-175 , January 2007

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