title: The influence of infliximab and adalimumab on the expression of apoptosis-related proteins in lamina propria mononuclear cells and enterocytes in Crohn's disease - an immunohistochemical study.
abstract: OBJECTIVE
  The aim of this study was to assess the influence of anti-TNF agents on the expression of apoptosis-related proteins in Crohn's disease (CD) patients.
  
  
  METHODS
  The clinical, biochemical and endoscopic activity of CD was assessed with the use of tissue sampling before the initiation of therapy and after induction doses of infliximab and adalimumab. Additionally, the immunohistochemical expression of active caspase 3, TNFR1, Fas, Bcl-2, Bax, CD4 and CD8 proteins was estimated. Patients achieving deep remission were considered as responders.
  
  
  RESULTS
  Of the 35 patients qualified for the study, 60% achieved deep remission. In those patients, a significant decrease in the number of CD4 and CD8 positive cells was noted. Also observed was a significant increase in the expression of active caspase 3 in lamina propria mononuclear cells, which correlated with an increase of the pro-apoptotic Bax/Bcl-2 ratio. No change in Fas and TNFR1 expression was observed in those cells. Moreover, there was a significant decrease in active caspase 3 expression in enterocytes, observed independently of the Bax/Bcl-2 ratio. This correlated with a change in TNFR1 expression. No significant changes in the expression of the investigated proteins were noted in non-responders group.
  
  
  CONCLUSIONS
  The efficacy of anti-TNF antibodies is, at least partly, dependent on apoptosis modulation. In lamina propria mononuclear cells, the increase of apoptosis is probably the result of the induction of the intrinsic pathway mediated by Bcl-2 family proteins. In enterocytes - the decrease of apoptosis is mediated by the extrinsic pathway, probably via TNFR1.
authors.affiliation: Department of Gastroenterology, University of Medical Sciences, Poznan, Poland. piotr.eder@op.pl
authors.forename: Piotr
authors.initials: P
authors.lastname: Eder
authors.forename: Liliana
authors.initials: L
authors.lastname: Lykowska-Szuber
authors.forename: Iwona
authors.initials: I
authors.lastname: Krela-Kazmierczak
authors.forename: Kamila
authors.initials: K
authors.lastname: Stawczyk-Eder
authors.forename: Maciej
authors.initials: M
authors.lastname: Zabel
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Linke
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D053148:Caspase 3 / Q000032:analysis; D002452:Cell Count; D003424:Crohn Disease / Q000188:drug therapy* / Q000473:pathology; D020895:Enterocytes / Q000737:chemistry / Q000187:drug effects*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D060828:Induction Chemotherapy; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000032:analysis; D055815:Young Adult; D051028:bcl-2-Associated X Protein / Q000032:analysis; D019014:fas Receptor / Q000032:analysis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C494826:BAX protein, human; D015704:CD4 Antigens; D016827:CD8 Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D047888:Receptors, Tumor Necrosis Factor, Type I; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D000069285:Infliximab; D053148:Caspase 3; D000068879:Adalimumab