| Anti-inflammatory role of glycine in reducing rodent postoperative inflammatory ileus. | |
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MedLine Citation:
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PMID: 20939853 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Inflammatory events within the intestinal muscularis, including macrophage activation and leukocyte recruitment, have been demonstrated to participate in causing postoperative ileus. Recently, glycine has gained attention due to its beneficial immunomodulatory effects in transplantation, shock and sepsis. METHODS: Muscularis glycine receptors were investigated by immunohistochemistry. Gastrointestinal motility was assessed by in vivo transit distribution histograms with calculated geometric center analysis and jejunal circular smooth muscle contractility in a standard organ bath. The impact of glycine on the muscularis inflammatory responses to surgical manipulation of the intestine were measured by real-time PCR, nitric oxide Griess reaction, prostaglandin ELISA, Luminex and histochemistry. KEY RESULTS: Glycine-gated chloride channels were immunohistochemically localized to muscularis macrophages and postoperative infiltrating leukocytes. Preoperative glycine treatment significantly improved postoperative gastrointestinal transit and jejunal circular muscle contractility. Preoperative glycine injection significantly reduced the induction of interleukin-6 (IL-6), tumor necrosis factor-α, inducible nitric oxide synthase and intercellular adhesion molecule-1 mRNAs, which was associated with the attenuation in postoperative leukocyte recruitment. Nitric oxide and prostanoid release from the postsurgical inflamed muscularis was diminished by glycine. The secretion of the inflammatory proteins IL-6, monocyte chemotactic protein-1/chemokine ligand 2 and macrophage inflammatory protein-1α/chemokine ligand 3 were also significantly decreased by glycine pretreatment. CONCLUSIONS & INFERENCES: The data indicate that preoperative glycine reduces postoperative ileus via the early attenuation of primal inflammatory events within the surgically manipulated gut wall. Therapeutic modulation of resident macrophages by glycine is a potential novel pharmacological target for the prevention of postoperative ileus. |
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Authors:
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B Stoffels; A Türler; J Schmidt; A Nazir; T Tsukamoto; B A Moore; C Schnurr; J C Kalff; A J Bauer |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-01 |
Journal Detail:
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Title: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Volume: 23 ISSN: 1365-2982 ISO Abbreviation: Neurogastroenterol. Motil. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-08 Completed Date: 2011-03-24 Revised Date: 2012-01-04 |
Medline Journal Info:
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Nlm Unique ID: 9432572 Medline TA: Neurogastroenterol Motil Country: England |
Other Details:
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Languages: eng Pagination: 76-87, e8 Citation Subset: IM |
Copyright Information:
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© 2010 Blackwell Publishing Ltd. |
Affiliation:
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Department of Medicine/Gastroenterology, University of Pittsburgh, Pittsburgh, PA 15261, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Inflammatory Agents* / pharmacology, therapeutic use Glycine* / pharmacology, therapeutic use Ileus* / immunology, pathology Inflammation / drug therapy*, immunology Male Mice Mice, Inbred C57BL Postoperative Complications / drug therapy*, immunology Rats Receptors, Glycine / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DK02488/DK/NIDDK NIH HHS; P50 GM053789-100009/GM/NIGMS NIH HHS; P50-GM-53789/GM/NIGMS NIH HHS; R01 DK068610-05/DK/NIDDK NIH HHS; R01 GM058241-05/GM/NIGMS NIH HHS; R01 GM058241-09/GM/NIGMS NIH HHS; R01-DK068610/DK/NIDDK NIH HHS; R01-GM58241/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents; 0/Receptors, Glycine; 56-40-6/Glycine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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