GDNF protects enteric glia from apoptosis: evidence for an autocrine loop
1 Department of Gastroenterology, Endocrinology and Metabolism, University of Gießen und Marburg GmbH, Site Marburg, Baldingerstraße, 35037 Marburg, Germany
2 Department of Internal Medicine I (Gastroenterology), University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany
BMC Gastroenterology 2012, 12:6 doi:10.1186/1471-230X-12-6Published: 17 January 2012
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.
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.
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.
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.