title: Intestinal intraepithelial lymphocyte derived angiotensin converting enzyme modulates epithelial cell apoptosis.
abstract: OBJECTIVE
  Intestinal adaptation in short bowel syndrome (SBS) consists of increased epithelial cell (EC) proliferation as well as apoptosis. Previous microarray analyses of intraepithelial lymphocytes (IEL) gene expression after SBS showed an increased expression of angiotensin converting enzyme (ACE). Because ACE has been shown to promote alveolar EC apoptosis, we examined if IEL-derived ACE plays a role in intestinal EC apoptosis.
  
  
  METHODS
  Mice underwent either a 70% mid-intestinal resection (SBS group) or a transection (Sham group) and were studied at 7 days. ACE expression was measured, and ACE inhibition (ACE-I, enalaprilat) was used to assess ACE function.
  
  
  RESULTS
  IEL-derived ACE was significantly elevated in SBS mice. The addition of an ACE-I to SBS mice resulted in a significant decline in EC apoptosis. To address a possible mechanism, tumor necrosis factor alpha (TNF-alpha) mRNA expression was measured. TNF-alpha was significantly increased in SBS mice, and decreased with ACE-I. Interestingly, ACE-I was not able to decrease EC apoptosis in TNF-alpha knockout mice.
  
  
  CONCLUSIONS
  This study shows a previously undescribed expression of ACE by IEL. SBS was associated with an increase in IEL-derived ACE. ACE appears to be associated with an up-regulation of intestinal EC apoptosis. ACE-I significantly decreased EC apoptosis.
authors.affiliation: Department of Surgery, Section of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Wildhaber
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: E Q
authors.initials: EQ
authors.lastname: Haxhija
authors.forename: A U
authors.initials: AU
authors.lastname: Spencer
authors.forename: D H
authors.initials: DH
authors.lastname: Teitelbaum
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007422:Intestines / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000601:surgery; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012778:Short Bowel Syndrome / Q000201:enzymology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D016207:Cytokines; D053222:Fas Ligand Protein; C491899:Fas protein, mouse; D018836:Inflammation Mediators; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D007703:Peptidyl-Dipeptidase A