title: Proinflammatory cytokines increase glial fibrillary acidic protein expression in enteric glia.
abstract: BACKGROUND
  Enteric glia protect the integrity of the gut, as loss of enteric glial fibrillary acidic protein (GFAP) positive (+) glia leads to a haemorrhagic jejunoileitis. Crohn's disease (CD) and necrotising enterocolitis (NEC) show pathological changes in enteric glia. Therefore, factors controlling GFAP+ enteric glia are of great interest. The aim of the present study was to characterise enteric glia and determine the effect of interleukin 1beta (IL-1beta), interleukin 4 (IL-4), tumour necrosis factor alpha (TNF-alpha), and lipopolysaccharides (LPS) on cultured enteric glia.
  
  
  METHODS
  Dissected rat colon and cultured enteric glia cells were double labelled with anti-GFAP and anti-S-100 antibodies. For regulatory studies, enteric glia cells were treated with cytokines and LPS. Proliferation was assayed using bromodeoxyuridine (BrdU) and mitosis of enteric glia was blocked by demecolcine.
  
  
  RESULTS
  We were able to distinguish GFAP negative (-) from GFAP+ glia subtypes in situ and in primary cultures. Incubation of cells with IL-1beta, TNF-alpha, and LPS led to a significant increase in GFAP+ enteric glia while IL-4 had no effect on GFAP expression. After incubation with IL-1beta, total intracellular GFAP of enteric glia cells was increased. Upregulation of GFAP+ enteric glia could also be observed after stimulation with IL-1beta on blocking mitosis. BrdU uptake in stimulated enteric glia showed no increased proliferation rate.
  
  
  CONCLUSIONS
  Two different types of enteric glia based on GFAP expression exist in the gut. Proinflammatory cytokines and LPS cause a dramatic increase in GFAP+ enteric glia. This suggests that cytokines play an important role in controlling GFAP+ enteric glia which might in turn be involved in modulating the integrity of the bowel during inflammation.
authors.affiliation: Department of Medicine I (Gastroenterology), University of Ulm, Albert-Einstein-Allee 11, 89069 Ulm, Germany.
authors.forename: G B T
authors.initials: GB
authors.lastname: von Boyen
authors.forename: M
authors.initials: M
authors.lastname: Steinkamp
authors.forename: M
authors.initials: M
authors.lastname: Reinshagen
authors.forename: K-H
authors.initials: KH
authors.lastname: Schäfer
authors.forename: G
authors.initials: G
authors.lastname: Adler
authors.forename: J
authors.initials: J
authors.lastname: Kirsch
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003092:Colitis / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000294:innervation* / Q000473:pathology; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017615:Enteric Nervous System / Q000378:metabolism* / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4