title: Infliximab restores the balance between pro- and anti-apoptotic proteins in regressing psoriatic lesions.
abstract: BACKGROUND
  Psoriasis and psoriatic arthritis are treated very efficaciously with infliximab, a chimaeric human-murine antitumour necrosis factor (TNF)-α antibody. As we reported earlier, infliximab, besides its anti-inflammatory properties, induces a caspase-independent programmed cell death of psoriatic keratinocytes.
  
  
  OBJECTIVE
  To elucidate this finding further, we investigated the epidermal expression of proteins involved in the mitochondria-dependent (intrinsic) pathway of cell death.
  
  
  METHODS
  Quantification of proteins with pro- (p53, AIF, Bax) and anti-apoptotic functions (Bcl-2, Bcl-XL) and of NF-κB was performed by means of immunohistochemistry and digital image analysis of the staining of nonlesional skin and lesional psoriatic skin from patients treated with infliximab at weeks 0, 2 and 6.
  
  
  RESULTS
  Serial biopsies from psoriatic plaques of samples taken at days 0, 5, 14 and 21 of therapy demonstrated a significant downregulation of anti-apoptotic proteins Bcl-2, Bcl-XL and NF-κB during treatment and, in parallel, a significant upregulation of pro-apoptotic proteins p53, Bax and AIF. These differences in expression correlated with decreases in epidermal thickness and clinical outcome (Psoriasis Area and Severity Index). At day 21, expression levels of apoptosis-related proteins in lesional skin approximated those found in nonlesional skin.
  
  
  CONCLUSIONS
  Our data therefore suggest that TNF-targeting agents may induce the regression of psoriasis at least in part by normalizing the expression of apoptosis-related proteins in lesional keratinocytes.
authors: Departments of Dermatology and Histopathology, University Hospital of Heraklion, University of Crete, 71110 Heraklion, Crete, Greece. krkras@med.uoc.gr
authors: G
authors: G
authors: Kokolakis
authors: E
authors: E
authors: Giannikaki
authors: E
authors: E
authors: Stathopoulos
authors: G
authors: G
authors: Avramidis
authors: A D
authors: AD
authors: Tosca
authors: S
authors: S
authors: Krüger-Krasagakis
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001706:Biopsy; D020169:Caspases / Q000378:metabolism; D003879:Dermatologic Agents / Q000627:therapeutic use*; D015536:Down-Regulation; D004817:Epidermis / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D000069285:Infliximab; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D051033:Apoptosis Inducing Factor; D051017:Apoptosis Regulatory Proteins; D003879:Dermatologic Agents; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D000069285:Infliximab; D020169:Caspases