title: Direct effect of infliximab on intestinal mucosa sustains mucosal healing: exploring new mechanisms of action.
abstract: BACKGROUND
  Infliximab is effective in inflammatory bowel disease through several mechanisms, possibly acting at the mucosal level.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Internal Medicine Department, Gastroenterology Division, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Petito
authors.affiliation: Internal Medicine Department, Gastroenterology Division, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Loris Riccardo
authors.initials: LR
authors.lastname: Lopetuso
authors.affiliation: Institute of Pathology, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Arena
authors.affiliation: Institute of Pathology, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Egidio
authors.initials: E
authors.lastname: Stigliano
authors.affiliation: Institute of Pathology, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Alma
authors.initials: A
authors.lastname: Boninsegna
authors.affiliation: Internal Medicine Department, Gastroenterology Division, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bibbò
authors.affiliation: Institute of Hygiene, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Poscia
authors.affiliation: Surgery Department, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Alfieri
authors.affiliation: Surgery Department, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Rosa
authors.affiliation: Internal Medicine Department, Gastroenterology Division, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Amato
authors.affiliation: Internal Medicine Department, Gastroenterology Division, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cammarota
authors.affiliation: Internal Medicine Department, Gastroenterology Division, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Papa
authors.affiliation: Institute of Pathology, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sgambato
authors.affiliation: Internal Medicine Department, Gastroenterology Division, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gasbarrini
authors.affiliation: Internal Medicine Department, Gastroenterology Division, Catholic University of Sacred Heart, Rome, Italy. Electronic address: francoscaldaferri@gmail.com.
authors.forename: Franco
authors.initials: F
authors.lastname: Scaldaferri
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001706:Biopsy; D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006801:Humans; D000069285:Infliximab / Q000494:pharmacology*; D020381:Interleukin-17 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology*; D020935:MAP Kinase Signaling System; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D015820:Cadherins; D016207:Cytokines; D005765:Gastrointestinal Agents; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab
keywords: Cellular proliferation; Infliximab; Mucosal healing; TNF-α; Wound repair