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Dissertation/Thesis Abstract

Enteric Glia Cells Attenuate Cytomix-induced Intestinal Epithelial Barrier Breakdown
by Cheadle, Gerald Andrew, M.S., University of California, San Diego, 2012, 44; 1508862
Abstract (Summary)

Intestinal barrier failure may lead to a systemic inflammatory response and distant organ injury in patients following severe injury. Enteric Glia Cells (EGCs) have been shown to play an important role in maintaining gut barrier integrity through secretion of S-nitrosoglutathione (GSNO). We have recently shown than Vagal nerve stimulation (VNS) increases EGC activation, which was associated with improved gut barrier integrity. Thus, we sought to study the mechanism by which VNS prevents epithelial barrier injury using an in vitro model. We postulated that VNS activates EGCs via a nicotinic cholinergic signaling mechanism, causing secretion of GSNO, resulting in improved epithelial barrier function through improved expression of intestinal tight junction proteins.

To determine the effects of EGCs on epithelial cells, epithelial cell lines were co-cultured with EGCs or incubated with GSNO and stimulated with Cytomix (TNF-α, INF-γ, IL-1β). We found that EGCs and GSNO were able to attenuate Cytomix-induced monolayer permeability through improved expression of the tight junction proteins ZO-1, occludin, and phosphorylated Myosin Light Chain (P-MLC). EGCs were treated with nicotine to determine if a nicotinic cholinergic agonist would induce their activation as a potential signaling mechanism linking EGCs with VNS-induced barrier protection. Treatment with nicotine resulted in EGC activation, as evidenced by an increase GFAP expression, and was associated with improved barrier function in epithelial monolayers exposed to inflammatory insults. Thus, therapies that increase EGC activation, such as VNS, limit intestinal barrier failure and may be a novel treatment strategy in patients following severe injury.

Indexing (document details)
Advisor: Coimbra, Raul
Commitee: Kronenberg, Mitch, Troemel, Emily
School: University of California, San Diego
Department: Biology
School Location: United States -- California
Source: MAI 50/05M, Masters Abstracts International
Subjects: Cellular biology
Keywords: Cholinergic signaling, Enteric glia, Intestinal failure, Nitrosoglutathione
Publication Number: 1508862
ISBN: 978-1-267-28818-9
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