title: Activation of Myenteric Glia during Acute Inflammation In Vitro and In Vivo.
abstract: BACKGROUND
  Enteric glial cells (EGCs) are the main constituent of the enteric nervous system and share similarities with astrocytes from the central nervous system including their reactivity to an inflammatory microenvironment. Previous studies on EGC pathophysiology have specifically focused on mucosal glia activation and its contribution to mucosal inflammatory processes observed in the gut of inflammatory bowel disease (IBD) patients. In contrast knowledge is scarce on intestinal inflammation not locally restricted to the mucosa but systemically affecting the intestine and its effect on the overall EGC network.
  
  
  RESULTS
  In this study, we analyzed the biological effects of a systemic LPS-induced hyperinflammatory insult on overall EGCs in a rat model in vivo, mimicking the clinical situation of systemic inflammation response syndrome (SIRS). Tissues from small and large intestine were removed 4 hours after systemic LPS-injection and analyzed on transcript and protein level. Laser capture microdissection was performed to study plexus-specific gene expression alterations. Upon systemic LPS-injection in vivo we observed a rapid and dramatic activation of Glial Fibrillary Acidic Protein (GFAP)-expressing glia on mRNA level, locally restricted to the myenteric plexus. To study the specific role of the GFAP subpopulation, we established flow cytometry-purified primary glial cell cultures from GFAP promotor-driven EGFP reporter mice. After LPS stimulation, we analyzed cytokine secretion and global gene expression profiles, which were finally implemented in a bioinformatic comparative transcriptome analysis. Enriched GFAP+ glial cells cultured as gliospheres secreted increased levels of prominent inflammatory cytokines upon LPS stimulation. Additionally, a shift in myenteric glial gene expression profile was induced that predominantly affected genes associated with immune response.
  
  
  CONCLUSIONS
  Our findings identify the myenteric GFAP-expressing glial subpopulation as particularly susceptible and responsive to acute systemic inflammation of the gut wall and complement knowledge on glial involvement in mucosal inflammation of the intestine.
authors.affiliation: Department of Tissue Engineering and Regenerative Medicine (TERM), University Hospital Wuerzburg, Wuerzburg, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Rosenbaum
authors.affiliation: Department of Anaesthesia and Critical Care, University of Wuerzburg, Wuerzburg Germany.
authors.forename: Martin Alexander
authors.initials: MA
authors.lastname: Schick
authors.affiliation: Department of Anaesthesia and Critical Care, University of Wuerzburg, Wuerzburg Germany.|Department of Anesthesiology and Intensive Care Medicine, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: Wollborn
authors.affiliation: Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heider
authors.affiliation: Interdisciplinary Centre for Clinical Research (IZKF), University Hospital Wuerzburg, Wuerzburg, Germany.
authors.forename: Claus-Jürgen
authors.initials: CJ
authors.lastname: Scholz
authors.affiliation: Department of Bioinformatics, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Cecil
authors.affiliation: Department of Human Molecular Genetics and nCounter Core Facility, Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Niesler
authors.affiliation: Carl-Ludwig-Institute for Physiology, University of Leipzig, Leipzig, Germany.|Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Goettingen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hirrlinger
authors.affiliation: Department of Tissue Engineering and Regenerative Medicine (TERM), University Hospital Wuerzburg, Wuerzburg, Germany.|Translational Center 'Regenerative Therapies for Oncology and Musculoskeletal Diseases' (TZKME), Branch of the Fraunhofer Institute Interfacial Engineering and Biotechnology (IGB), Wuerzburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Walles
authors.affiliation: Department of Tissue Engineering and Regenerative Medicine (TERM), University Hospital Wuerzburg, Wuerzburg, Germany.|Translational Center 'Regenerative Therapies for Oncology and Musculoskeletal Diseases' (TZKME), Branch of the Fraunhofer Institute Interfacial Engineering and Biotechnology (IGB), Wuerzburg, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Metzger
mesh_terms: D000208:Acute Disease; D000818:Animals; D020869:Gene Expression Profiling; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D009197:Myenteric Plexus / Q000473:pathology*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D018805:Sepsis / Q000473:pathology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; C528900:glial fibrillary astrocytic protein, mouse