Abstract

Background: Infliximab is effective in inflammatory bowel disease through several mechanisms, possibly acting at the mucosal level. Aim: To assess the role of infliximab on intestinal mucosa and whether it contributes to mucosal healing. Methods: Human colonic mucosal biopsies were incubated with or without infliximab. Cultured biopsies were evaluated for histological staining, CD68, CD3, E-cadherin and phospho-extracellular signal-regulated kinases (ERK) expression, and apoptosis. A scratch assay and MTT assay were performed with Caco2 cells in the presence of infliximab and/or tumour necrosis factor (TNF)-α or treated with supernatants obtained from human peripheral blood mononuclear cells or human intestinal fibroblasts treated with TNF-α and infliximab alone or in association. Results: Infliximab-treated biopsies displayed a better histological appearance, reduced inflammation with an increase of E-cadherin, phospho-ERK and apoptosis. Supernatants showed lower TNF-α, IL-17, IL-6 and IL-8 concentration, with an increase in fibroblast-growth-factor. Motility at scratch assay and proliferation at MTT assay of Caco2 cells displayed differential modulation by TNF-α and infliximab, directly or through supernatants of human intestinal fibroblasts and human peripheral blood mononuclear cells exposed to them. Conclusion: Infliximab contributes to the mucosal healing process by acting directly at an intestinal mucosal level; infliximab indirectly affects epithelial cell migration and proliferation by acting on both fibroblasts and leukocytes.
Lingua originaleEnglish
pagine (da-a)391-398
Numero di pagine8
RivistaDIGESTIVE AND LIVER DISEASE
Volume48
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • Apoptosis
  • Biopsy
  • Caco-2 Cells
  • Cadherins
  • Cell Proliferation
  • Cellular proliferation
  • Colitis, Ulcerative
  • Cytokines
  • Fibroblasts
  • Gastroenterology
  • Gastrointestinal Agents
  • Hepatology
  • Humans
  • Infliximab
  • Interleukin-17
  • Intestinal Mucosa
  • MAP Kinase Signaling System
  • Mucosal healing
  • TNF-α
  • Tumor Necrosis Factor-alpha
  • Wound Healing
  • Wound repair

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