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Enhanced Human β-Defensin-2 (hBD-2) Expression by Corticosteroids Is Independent of NF-κB in Colonic Epithelial Cells (CaCo2)

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Abstract

β-Defensins are small cationic peptides with antimicrobial properties that contribute to innate host defense. Unlike human β-defensin-1 (hBD-1), which is produced constitutively, human β-defensin-2 (hBD-2) is expressed after adequate stimulation by cytokines and/or bacterial endotoxins in epithelial tissue and mononuclear phagocytes but may be deficient in patients with Crohn’s disease. To further elucidate the role of the intestinal epithelium in antimicrobial host defense, gene regulation of hBD-2 and the interaction with NF-κB were analyzed in a cell culture model. Human colonic epithelial cells (CaCo2) were stimulated by pro-inflammatory cytokines (IL-1β, TNF-α, IF-γ) to induce hBD-2 mRNA transcription. Interactions with NF-κB were analyzed using specific inhibitors (sulfasalazine, gliotoxine, dexamethasone) at different concentrations. Defensin mRNA expression was quantified by competitive RT-PCR and antibacterial capacity of supernatants was determined by an antimicrobial assay. HBD-2 mRNA transcription and antimicrobial activity of CaCo2 cells were induced by stimulation with pro-inflammatory cytokines. Induction was not inhibited by sulfasalazine or gliotoxine, whereas dexamethasone further enhanced both gene transcription and antimicrobial capacity. The lack of inhibition of induced hBD-2 expression by specific NF-κB antagonists suggests an additional pathway of activation, independent of NF-κB. The induction of hBD-2 expression in cytokine-stimulated CaCo2 cells by corticosteroids indicates further immunomodulatory ability of steroid hormones not yet understood.

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Authors and Affiliations

  1. Divisions of Gastroenterology, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck

    T. Witthöft MD, C. S. Pilz MD & D. Ludwig MD

  2. Divisions of Nephrology, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck

    M. Nitschke MD

  3. Department of Medicine, Robert Bosch Hospital, Stuttgart, Germany

    K. Fellermann MD & E. F. Stange MD

  4. Department of Gastroenterology, University Clinics of Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, D-23538, Lübeck, Germany

    D. Ludwig MD

Authors
  1. T. Witthöft MD
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  2. C. S. Pilz MD
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  3. K. Fellermann MD
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  4. M. Nitschke MD
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  5. E. F. Stange MD
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  6. D. Ludwig MD
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Correspondence to D. Ludwig MD.

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Witthöft, T., Pilz, C.S., Fellermann, K. et al. Enhanced Human β-Defensin-2 (hBD-2) Expression by Corticosteroids Is Independent of NF-κB in Colonic Epithelial Cells (CaCo2). Dig Dis Sci 50, 1252–1259 (2005). https://doi.org/10.1007/s10620-005-2768-5

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  • DOI: https://doi.org/10.1007/s10620-005-2768-5

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