Distribution of enteric glia and GDNF during gut inflammation

Georg Bt Von Boyen,Carolin Pflüger,Nadine Schulte,Martin Steinkamp,Christoph Hartmann,Ulrike Spaniol

doi:10.1186/1471-230x-11-3

Georg Bt Von Boyen, Carolin Pflüger + Show 4 more

Open Access

https://doi.org/10.1186/1471-230x-11-3

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Abstract

BackgroundThe enteric glia network may be involved in the pathogenesis of inflammatory bowel disease (IBD). Enteric glia cells (EGCs) are the major source of glial-derived neurotrophic factor (GDNF), which regulates apoptosis of enterocytes. The aim of the study was to determine the distribution of EGCs and GDNF during gut inflammation and to elucidate a possible diminished enteric glia network in IBD.MethodsThe expression of glial fibrillary acidic protein (GFAP) in colonic biopsies of patients with IBD, controls and patients with infectious colitis was detected by immunohistochemistry and Western blot. Tissue GDNF levels were measured by ELISA.ResultsThe expression of GFAP and GDNF in the mucosal plexus is highly increased in the inflamed colon of patients with ulcerative colitis (UC) and infectious colitis. Although the GDNF and GFAP content are increased in Crohn's disease (CD), it is significantly less. Additionally the non-inflamed colon of CD patients showed a reduced GFAP and no GDNF expression compared to controls and the non-inflamed colon of UC patients.ConclusionsGFAP and GDNF as signs of activated EGCs are increased in the inflamed mucosa of patients with UC and infectious colitis, which underline an unspecific role of EGC in the regulation of intestinal inflammation. The reduced GFAP and GDNF content in the colon of CD patients suggest a diminished EGC network in this disease. This might be a part of the pathophysiological puzzle of CD.

Highlights

The enteric glia network may be involved in the pathogenesis of inflammatory bowel disease (IBD)
We could show that enteric glia cells (EGC) secrete glial-derived neurotrophic factor (GDNF) whose production is increased during intestinal inflammation and could act to protect intestinal epithelial cells from cytokine-induced apoptosis [12,13,14]
Inflamed and non-inflamed colonic biopsies were taken from 35 patients with Crohn’s disease (CD) (15 female/20 male; mean age 31 years; range 21 to 48 years) and from 30 patients with ulcerative colitis (UC) (12 female/18 male; mean age 34 years; range 24 to 52 years). 15 patients with CD were in clinical remission (Crohn’s Disease Activity Index CDAI < 150) and 20 patients showed clinically a mild flare (CDAI > 150). 10 patients with UC were in remission defined by a Colitis Activity Index (CAI) of 0, whereas the other 20 patients suffered from a flare, CAI > 4

Summary

Introduction

The enteric glia network may be involved in the pathogenesis of inflammatory bowel disease (IBD). Enteric glia cells (EGCs) are the major source of glial-derived neurotrophic factor (GDNF), which regulates apoptosis of enterocytes. There is no definite cure for these diseases and the etiology of IBD remains unknown there are some new insights into its pathophysiology Both CD and UC are characterized by a significant increase of proinflammatory cytokines in the gut, which trigger and support the inflammatory processes [2]. It was shown that nitric oxide metabolite S-nitrosogluthatione (GSNO), a novel potent inducer of intestinal barrier function in human colon [11] is secreted by EGCs. we could show that EGCs secrete glial-derived neurotrophic factor (GDNF) whose production is increased during intestinal inflammation and could act to protect intestinal epithelial cells from cytokine-induced apoptosis [12,13,14]

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