title: Effect of tumor necrosis factor-α blockade on mucosal addressin cell-adhesion molecule-1 in Crohn's disease.
abstract: BACKGROUND
  Mucosal addressin cell-adhesion molecule (MAdCAM)-1, which is overexpressed on gut endothelium in active Crohn's disease (CD), promotes intestinal recruitment of integrin α(4)β(7)(*) T cells that sustain chronic inflammation. As tumor necrosis factor alpha (TNF)-α, a cytokine centrally involved in CD, modulates gut endothelial adhesion molecules, we here explored the in vivo and ex vivo effects of TNF-α blockade on MAdCAM-1 expression in CD.
  
  
  METHODS
  MAdCAM-1 was determined by immunoblotting in colonic biopsies collected before and 10 weeks after either infliximab or adalimumab treatment in CD patients, and in CD biopsies incubated with either infliximab or adalimumab or control IgG(1). Integrin β(7)(*) circulating T cells were analyzed by flow cytometry.
  
  
  RESULTS
  MAdCAM-1 significantly decreased after either infliximab or adalimumab treatment in responder but not in nonresponder patients. In parallel, an increase of circulating β(7)(*) T cells was found in responder patients only. A marked downregulation of MAdCAM-1 was observed in CD biopsies cultured with either infliximab or adalimumab in comparison to IgG(1)-treated biopsies.
  
  
  CONCLUSIONS
  Our findings showing that MAdCAM-1 is downregulated by TNF-α blockade point to a novel mechanism of action of anti-TNF-α antibodies in CD.
authors: Centre for Immunology and Infectious Disease, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK.
authors: Paolo
authors: P
authors: Biancheri
authors: Antonio
authors: A
authors: Di Sabatino
authors: Laura
authors: L
authors: Rovedatti
authors: Paolo
authors: P
authors: Giuffrida
authors: Sandra A
authors: SA
authors: Calarota
authors: Stefania
authors: S
authors: Vetrano
authors: Francesca
authors: F
authors: Vidali
authors: Alessandra
authors: A
authors: Pasini
authors: Silvio
authors: S
authors: Danese
authors: Gino R
authors: GR
authors: Corazza
authors: Thomas T
authors: TT
authors: MacDonald
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D015815:Cell Adhesion Molecules; D003106:Colon / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D004334:Drug Administration Schedule; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D000069285:Infliximab; D039641:Integrin beta Chains / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009088:Mucoproteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D039641:Integrin beta Chains; C504265:MADCAM1 protein, human; D009088:Mucoproteins; C091368:integrin beta7; D000069285:Infliximab; D000068879:Adalimumab