title: Epithelial apoptosis: cause or consequence of ulcerative colitis?
abstract: OBJECTIVE
  Epithelial apoptosis rates are increased in ulcerative colitis (UC). The increased apoptosis rate could expose mucosal cells to luminal pathogens and thereby be regarded as a primary pathogenic factor in UC. On the other hand, the local inflammatory reaction could cause epithelial apoptosis secondary to the release of cytotoxic mediators. If apoptosis is a primary defect, apoptosis rates could influence the degree of spreading of inflammation and the clinical course of UC. If apoptosis is a side effect of local inflammation, apoptosis rates would be expected only to correlate with the degree of local inflammation. The aim of the study was to investigate the relationship between epithelial apoptosis and clinical characteristics of UC.
  
  
  METHODS
  Twenty patients with UC (12 with active disease) and 20 control subjects were included. Freshly isolated colonic epithelial cells were cultured. Apoptosis was determined by flow cytometry. Cells were stimulated with Fas ligand. The disease was characterized by endoscopic findings, microscopic inflammation grade, surrogate markers of disease activity (hemoglobin level, white blood cell count, C-reactive protein, or albumin), and the clinical course 6 months after biopsy.
  
  
  RESULTS
  Epithelial apoptosis correlated with local inflammation, both macroscopic (p< 0.02) and microscopic (p< 0.008). Disease extent, disease course, or surrogate markers of disease activity did not correlate with apoptosis rate. However, increased microscopic inflammation inversely correlated with apoptosis response to the Fas ligand (p< 0.06).
  
  
  CONCLUSIONS
  The epithelial apoptosis rate is influenced primarily by the local inflammatory response. Colonocytes upregulate cytoprotective mediators that decrease apoptosis susceptibility during active UC.
authors: Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Denmark. jseidelin@dadlnet.dk
authors: Jakob Benedict
authors: JB
authors: Seidelin
authors: Ole Haagen
authors: OH
authors: Nielsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001706:Biopsy; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012809:Colon, Sigmoid / Q000473:pathology; D003113:Colonoscopy; D004847:Epithelial Cells / Q000473:pathology*; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D012007:Rectum / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D053222:Fas Ligand Protein; D005938:Glucocorticoids; D011239:Prednisolone