title: Infliximab therapy downregulation of basic fibroblast growth factor/syndecan 1 link: a possible molecular pathway of mucosal healing in ulcerative colitis.
abstract: BACKGROUND
  It is known that syndecan 1 in inflammatory bowel diseases is able to migrate from epithelial basolateral site to the stromal area and apical surface of epithelium with a consequent activation and modulation of basic fibroblast growth factor (bFGF), and this process sustains mucosal healing of ulcers. On the other hand, tumour necrosis factor (TNF) α mucosal levels are directly related to the entity of the damage in these disorders. Aim of the study A 'post-hoc' retrospective study was performed to estimate mucosal TNF α in rectal biopsies of subjects with ulcerative colitis (UC) before and after effective infliximab therapy and its relationship with syndecan 1, bFGF and endoscopic mucosal healing.
  
  
  METHODS
  Paraffin-embedded rectal samples from 12 patients with UC responders to infliximab were analysed for TNF α, syndecan 1 and bFGF before and 6 months after therapy using a real-time reverse transcriptase polymersase chain reaction. Additionally, syndecan 1 location was evaluated by immunohistochemistry. Samples from 12 subjects with irritable bowel symptoms without endoscopic/histological abnormalities represented the control group. Mucosal healing induced by the treatment was defined by an endoscopic Mayo subscore changing from 2-3 to 0. ANOVA plus Student-Newman-Keuls was used for statistical analysis.
  
  
  RESULTS
  The authors found that in the active disease, an increase in TNF α (p<0.001) is accompanied by raised levels of both syndecan 1 (p<0.005) and bFGF (p<0.005) compared with the control group. Infliximab-induced TNF α decrease to levels similar to controls is associated with both endoscopic mucosal healing and adhesion molecule/growth factor significant reduction. Additionally, syndecan 1 location, which is predominant in the stromal cells and apical epithelium in the active disorder, is quite exclusively located at the basolateral epithelial area in both healed mucosa and controls.
  
  
  CONCLUSIONS
  Balanced interaction among TNF α inhibition by infliximab, syndecan 1 migration, bFGF repair modulation and final adhesion molecule reversal to its normal location might represent a suitable molecular pathway of endoscopic mucosal healing in UC.
authors.affiliation: Section of Gastroenterology, Department of Medical Sciences, University of Foggia, Foggia, Italy. enzo.ierardi@fastwenet.it
authors.forename: Enzo
authors.initials: E
authors.lastname: Ierardi
authors.forename: Floriana
authors.initials: F
authors.lastname: Giorgio
authors.forename: Mariangela
authors.initials: M
authors.lastname: Zotti
authors.forename: Rosa
authors.initials: R
authors.lastname: Rosania
authors.forename: Mariabeatrice
authors.initials: M
authors.lastname: Principi
authors.forename: Stefania
authors.initials: S
authors.lastname: Marangi
authors.forename: Nicola
authors.initials: N
authors.lastname: Della Valle
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Francesco
authors.forename: Alfredo
authors.initials: A
authors.lastname: Di Leo
authors.forename: Marcello
authors.initials: M
authors.lastname: Ingrosso
authors.forename: Carmine
authors.initials: C
authors.lastname: Panella
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D015536:Down-Regulation; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012007:Rectum / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053668:Syndecan-1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D012333:RNA, Messenger; D053668:Syndecan-1; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D000069285:Infliximab