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Activation of Myenteric Glia during Acute Inflammation In Vitro and In Vivo

Please always quote using this URN: urn:nbn:de:bvb:20-opus-146544
  • 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 butBackground 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. Methods and 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. Conclusion and Significance 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.show moreshow less

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Metadaten
Author: Corinna Rosenbaum, Martin Alexander Schick, Jakob Wollborn, Andreas Heider, Claus-Jürgen Scholz, Alexander Cecil, Beate Niesler, Johannes Hirrlinger, Heike Walles, Marco Metzger
URN:urn:nbn:de:bvb:20-opus-146544
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Anästhesiologie (ab 2004)
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Medizinische Fakultät / Lehrstuhl für Tissue Engineering und Regenerative Medizin
Language:English
Parent Title (English):PLoS One
Year of Completion:2016
Volume:11
Issue:3
Pagenumber:e0151335
Source:PLoS ONE 11(3): e0151335. doi:10.1371/journal.pone.0151335
DOI:https://doi.org/10.1371/journal.pone.0151335
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:astrocytes; central nervous system; cytokines; gastrointestinal tract; gene expression; inflammation; inflammatory bowel disease; systemic inflammatory response syndrome
Release Date:2017/04/04
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2016
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung