title: GDNF protects enteric glia from apoptosis: evidence for an autocrine loop.
abstract: BACKGROUND
  Enteric glia cells (EGC) play an important role in the maintenance of intestinal mucosa integrity. During the course of acute Crohn's disease (CD), mucosal EGC progressively undergo apoptosis, though the mechanisms are largely unknown. We investigated the role of Glial-derived neurotrophic factor (GDNF) in the regulation of EGC apoptosis.
  
  
  METHODS
  GDNF expression and EGC apoptosis were determined by immunofluorescence using specimen from CD patients. In primary rat EGC cultures, GDNF receptors were assessed by western blot and indirect immunofluorescence microscopy. Apoptosis in cultured EGC was induced by TNF-α and IFN-γ, and the influence of GDNF on apoptosis was measured upon addition of GDNF or neutralizing anti-GDNF antibody.
  
  
  RESULTS
  Increased GDNF expression and Caspase 3/7 activities were detected in in specimen of CD patients but not in healthy controls. Moreover, inactivation of GDNF sensitized in EGC cell to IFN-γ/TNF-α induced apoptosis.
  
  
  CONCLUSIONS
  This study proposes the existence of an autocrine anti-apoptotic loop in EGC cells which is operative in Crohn's disease and dependent of GDNF. Alterations in this novel EGC self-protecting mechanism could lead to a higher susceptibility towards apoptosis and thus contribute to disruption of the mucosal integrity and severity of inflammation in CD.
authors.affiliation: Department of Gastroenterology, Endocrinology and Metabolism, University of Giessen und Marburg GmbH, Site Marburg, Baldingerstrasse, 35037 Marburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Steinkamp
authors.forename: Heike
authors.initials: H
authors.lastname: Gundel
authors.forename: Nadine
authors.initials: N
authors.lastname: Schulte
authors.forename: Ulrike
authors.initials: U
authors.lastname: Spaniol
authors.forename: Carolin
authors.initials: C
authors.lastname: Pflueger
authors.forename: Eugen
authors.initials: E
authors.lastname: Zizer
authors.forename: Georg B T
authors.initials: GB
authors.lastname: von Boyen
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D019898:Autocrine Communication / Q000502:physiology*; D001706:Biopsy; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D003106:Colon / Q000294:innervation* / Q000473:pathology; D003424:Crohn Disease / Q000378:metabolism / Q000473:pathology; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D023421:Models, Animal; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D005904:Glial Fibrillary Acidic Protein; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D053148:Caspase 3