Digestion

Original Paper

Galectin-3 Modulates Experimental Colitis

Lippert E. · Stieber-Gunckel M. · Dunger N. · Falk W. · Obermeier F. · Kunst C.

Author affiliations

Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany

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Digestion 2015;92:45-53

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: February 19, 2015
Accepted: May 11, 2015
Published online: July 17, 2015
Issue release date: August 2015

Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 0

ISSN: 0012-2823 (Print)
eISSN: 1421-9867 (Online)

For additional information: https://www.karger.com/DIG

Abstract

Background: We recently identified galectin-3 (gal-3) as a new and strong fibroblast activator produced by colonic epithelial cells. Very little is known about the influence of gal-3 in inflammatory bowel disease. We, therefore, investigated the impact of gal-3 on dextran sodium sulfate (DSS)-induced colitis in a mouse model. Methods: Colonic lamina propria fibroblasts of healthy controls were used for co-incubation studies of gal-3 with gal-1, TGF-β1, IFNγ, IL-4 and IL-10. Acute and chronic DSS colitis was induced by 3% DSS in drinking water in female Balb/c mice weighing 20-22 g. Recombinant gal-3 was expressed by the pET vector system and used for a 5-day treatment in different concentrations intraperitoneally. The distal third of the colon was used for histologic analysis. Colonic cytokine expression was determined by quantitative RT-PCR. Results: In vitro, gal-3 induced IL-8 secretion was significantly reduced by co-incubation with IL-10 (5 ng/ml) and IL-4 (10 ng/ml). Acute DSS-induced colitis was ameliorated by gal-3 treatment as indicated by increased colonic length and reduced weight loss compared to that of controls. In acute and chronic colitis, gal-3 treatment resulted in a significant suppression of colonic IL-6. Conclusion: Gal-3 significantly reduces inflammation in acute and chronic DSS colitis in mice indicating a potential role in intestinal inflammation.

© 2015 S. Karger AG, Basel




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References

  1. Lippert E, Falk W, Bataille F, Kaehne T, Naumann M, Goeke M, Herfarth H, Schoelmerich J, Rogler G: Soluble galectin-3 is a strong, colonic epithelial-cell-derived, lamina propria fibroblast-stimulating factor. Gut 2007;56:43-51.
  2. Lippert E, Gunckel M, Brenmoehl J, Bataille F, Falk W, Scholmerich J, Obermeier F, Rogler G: Regulation of galectin-3 function in mucosal fibroblasts: potential role in mucosal inflammation. Clin Exp Immunol 2008;152:285-297.
  3. Barondes SH, Castronovo V, Cooper DN, Cummings RD, Drickamer K, Feizi T, Gitt MA, Hirabayashi J, Hughes C, Kasai K: Galectins: a family of animal beta-galactoside-binding lectins. Cell 1994;76:597-598.
  4. Liu FT, Patterson RJ, Wang JL: Intracellular functions of galectins. Biochim Biophys Acta 2002;1572:263-273.
  5. Seetharaman J, Kanigsberg A, Slaaby R, Leffler H, Barondes SH, Rini JM: X-ray crystal structure of the human galectin-3 carbohydrate recognition domain at 2.1-A resolution. J Biol Chem 1998;273:13047-13052.
  6. Menon RP, Hughes RC: Determinants in the N-terminal domains of galectin-3 for secretion by a novel pathway circumventing the endoplasmic reticulum-Golgi complex. Eur J Biochem 1999;264:569-576.
  7. Henrick K, Bawumia S, Barboni EA, Mehul B, Hughes RC: Evidence for subsites in the galectins involved in sugar binding at the nonreducing end of the central galactose of oligosaccharide ligands: sequence analysis, homology modeling and mutagenesis studies of hamster galectin-3. Glycobiology 1998;8:45-57.
  8. Kim K, Mayer EP, Nachtigal M: Galectin-3 expression in macrophages is signaled by Ras/MAP kinase pathway and up-regulated by modified lipoproteins. Biochim Biophys Acta 2003;1641:13-23.
  9. Moutsatsos IK, Wade M, Schindler M, Wang JL: Endogenous lectins from cultured cells: nuclear localization of carbohydrate-binding protein 35 in proliferating 3T3 fibroblasts. Proc Natl Acad Sci U S A 1987;84:6452-6456.
  10. Flotte TJ, Springer TA, Thorbecke GJ: Dendritic cell and macrophage staining by monoclonal antibodies in tissue sections and epidermal sheets. Am J Pathol 1983;111:112-124.
  11. Davidson PJ, Davis MJ, Patterson RJ, Ripoche MA, Poirier F, Wang JL: Shuttling of galectin-3 between the nucleus and cytoplasm. Glycobiology 2002;12:329-337.
  12. Mehul B, Hughes RC: Plasma membrane targetting, vesicular budding and release of galectin 3 from the cytoplasm of mammalian cells during secretion. J Cell Sci 1997;110(Pt 10):1169-1178.
  13. Maeda N, Kawada N, Seki S, Arakawa T, Ikeda K, Iwao H, Okuyama H, Hirabayashi J, Kasai K, Yoshizato K: Stimulation of proliferation of rat hepatic stellate cells by galectin-1 and galectin-3 through different intracellular signaling pathways. J Biol Chem 2003;278:18938-18944.
  14. Sato S, Ouellet N, Pelletier I, Simard M, Rancourt A, Bergeron MG: Role of galectin-3 as an adhesion molecule for neutrophil extravasation during streptococcal pneumonia. J Immunol 2002;168:1813-1822.
  15. Akahani S, Nangia-Makker P, Inohara H, Kim HR, Raz A: Galectin-3: a novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family. Cancer Res 1997;57:5272-5276.
  16. Inohara H, Akahani S, Raz A: Galectin-3 stimulates cell proliferation. Exp Cell Res 1998;245:294-302.
  17. Rubinstein N, Ilarregui JM, Toscano MA, Rabinovich GA: The role of galectins in the initiation, amplification and resolution of the inflammatory response. Tissue Antigens 2004;​64:1-12.
  18. Liu SD, Lee S, La CA, Motran CC, Hahn BH, Miceli MC: Galectin-1-induced down-regulation of T lymphocyte activation protects (NZB × NZW) F1 mice from lupus-like disease. Lupus 2011;20:473-484.
  19. Motran CC, Molinder KM, Liu SD, Poirier F, Miceli MC: Galectin-1 functions as a Th2 cytokine that selectively induces Th1 apoptosis and promotes Th2 function. Eur J Immunol 2008;38:3015-3027.
  20. Matarrese P, Tinari N, Semeraro ML, Natoli C, Iacobelli S, Malorni W: Galectin-3 overexpression protects from cell damage and death by influencing mitochondrial homeostasis. FEBS Lett 2000;473:311-315.
  21. Dagher SF, Wang JL, Patterson RJ: Identification of galectin-3 as a factor in pre-mRNA splicing. Proc Natl Acad Sci U S A 1995;92:1213-1217.
  22. Hsu DK, Yang RY, Pan Z, Yu L, Salomon DR, Fung-Leung WP, Liu FT: Targeted disruption of the galectin-3 gene results in attenuated peritoneal inflammatory responses. Am J Pathol 2000;156:1073-1083.
  23. Obermeier F, Kojouharoff G, Hans W, Schölmerich J, Gross V, Falk W: Interferon-gamma (IFN-gamma)- and tumour necrosis factor (TNF)-induced nitric oxide as toxic effector molecule in chronic dextran sulphate sodium (DSS)-induced colitis in mice. Clin Exp Immunol 1999;116:238-245.
  24. Obermeier F, Strauch UG, Dunger N, Grunwald N, Rath HC, Herfarth H, Schölmerich J, Falk W: In vivo CpG DNA/toll-like receptor 9 interaction induces regulatory properties in CD4+CD62L+ T cells which prevent intestinal inflammation in the SCID transfer model of colitis. Gut 2005;54:1428-1436.
  25. Hans W, Schölmerich J, Gross V, Falk W: The role of the resident intestinal flora in acute and chronic dextran sulfate sodium-induced colitis in mice. Eur J Gastroenterol Hepatol 2000;12:267-273.
  26. Joo HG, Goedegebuure PS, Sadanaga N, Nagoshi M, von Bernstorff W, Eberlein TJ: Expression and function of galectin-3, a beta-galactoside-binding protein in activated T lymphocytes. J Leukoc Biol 2001;69:555-564.
  27. Breuilh L, Vanhoutte F, Fontaine J, van Stijn CM, Tillie-Leblond I, Capron M, Faveeuw C, Jouault T, van Die I, Gosset P, Trottein F: Galectin-3 modulates immune and inflammatory responses during helminthic infection: impact of galectin-3 deficiency on the functions of dendritic cells. Infect Immun 2007;75:5148-5157.
  28. Linden JR, De Paepe ME, Laforce-Nesbitt SS, Bliss JM: Galectin-3 plays an important role in protection against disseminated candidiasis. Med Mycol 2013;51:641-651.
  29. Wu SY, Yu JS, Liu FT, Miaw SC, Wu-Hsieh BA: Galectin-3 negatively regulates dendritic cell production of IL-23/IL-17-axis cytokines in infection by Histoplasma capsulatum. J Immunol 2013;190:3427-3437.
  30. Paclik D, Werner L, Guckelberger O, Wiedenmann B, Sturm A: Galectins distinctively regulate central monocyte and macrophage function. Cell Immunol 2011;271:97-103.
  31. Curciarello R, Steele A, Cooper D, MacDonald TT, Kruidenier L, Kudo T: The role of galectin-1 and galectin-3 in the mucosal immune response to citrobacter rodentium infection. PLoS One 2014;9:e107933.
  32. Yamamoto M, Yoshizaki K, Kishimoto T, Ito H: IL-6 is required for the development of Th1 cell-mediated murine colitis. J Immunol 2000;164:4878-4882.
  33. Tanaka T, Narazaki M, Kishimoto T: Anti-interleukin-6 receptor antibody, tocilizumab, for the treatment of autoimmune diseases. FEBS Lett 2011;585:3699-3709.
  34. Kang S, Tanaka T, Kishimoto T: Therapeutic uses of anti-interleukin-6 receptor antibody. Int Immunol 2015;27:21-29.
  35. Ito H, Takazoe M, Fukuda Y, Hibi T, Kusugami K, Andoh A, Matsumoto T, Yamamura T, Azuma J, Nishimoto N, Yoshizaki K, Shimoyama T, Kishimoto T: A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn's disease. Gastroenterology 2004;126:989-996; discussion 947.
  36. Brazowski E, Dotan I, Tulchinsky H, Filip I, Eisenthal A: Galectin-3 expression in pouchitis in patients with ulcerative colitis who underwent ileal pouch-anal anastomosis (IPAA). Pathol Res Pract 2009;205:551-558.
  37. Jensen-Jarolim E, Gscheidlinger R, Oberhuber G, Neuchrist C, Lucas T, Bises G, Radauer C, Willheim M, Scheiner O, Liu FT, Boltz-Nitulescu G: The constitutive expression of galectin-3 is downregulated in the intestinal epithelia of Crohn's disease patients, and tumour necrosis factor alpha decreases the level of galectin-3-specific mRNA in HCT-8 cells. Eur J Gastroenterol Hepatol 2002;14:145-152.
  38. Sturm A, Lensch M, André S, Kaltner H, Wiedenmann B, Rosewicz S, Dignass AU, Gabius HJ: Human galectin-2: novel inducer of T cell apoptosis with distinct profile of caspase activation. J Immunol 2004;173:3825-3837.
  39. Paclik D, Berndt U, Guzy C, Dankof A, Danese S, Holzloehner P, Rosewicz S, Wiedenmann B, Wittig BM, Dignass AU, Sturm A: Galectin-2 induces apoptosis of lamina propria T lymphocytes and ameliorates acute and chronic experimental colitis in mice. J Mol Med (Berl) 2008;86:1395-1406.
  40. Jensen-Jarolim E, Neumann C, Oberhuber G, Gscheidlinger R, Neuchrist C, Reinisch W, Zuberi RI, Penner E, Liu FT, Boltz-Nitulescu G: Anti-Galectin-3 IgG autoantibodies in patients with Crohn's disease characterized by means of phage display peptide libraries. J Clin Immunol 2001;21:348-356.
  41. Müller S, Schaffer T, Flogerzi B, Fleetwood A, Weimann R, Schoepfer AM, Seibold F: Galectin-3 modulates T cell activity and is reduced in the inflamed intestinal epithelium in IBD. Inflamm Bowel Dis 2006;12:588-597.
  42. Mobergslien A, Sioud M: Galectin-1 and -3 gene silencing in immature and mature dendritic cells enhances T cell activation and interferon-γ production. J Leukoc Biol 2012;91:461-467.
  43. Fermin Lee A, Chen HY, Wan L, Wu SY, Yu JS, Huang AC, Miaw SC, Hsu DK, Wu-Hsieh BA, Liu FT: Galectin-3 modulates Th17 responses by regulating dendritic cell cytokines. Am J Pathol 2013;183:1209-1222.
  44. Tribulatti MV, Figini MG, Carabelli J, Cattaneo V, Campetella O: Redundant and antagonistic functions of galectin-1, -3, and -8 in the elicitation of T cell responses. J Immunol 2012;188:2991-2999.
  45. Perše M, Cerar A: Dextran sodium sulphate colitis mouse model: traps and tricks. J Biomed Biotechnol 2012;2012:718617.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: February 19, 2015
Accepted: May 11, 2015
Published online: July 17, 2015
Issue release date: August 2015

Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 0

ISSN: 0012-2823 (Print)
eISSN: 1421-9867 (Online)

For additional information: https://www.karger.com/DIG


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