| Interleukin-13 protects mouse intestine from ischemia and reperfusion injury through regulation of innate and adaptive immunity. | |
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MedLine Citation:
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PMID: 21311412 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Ischemia-reperfusion (I/R) injury is a major factor leading to intestinal dysfunction or graft loss after intestinal surgery or transplantation. This study investigated the cytoprotective effects and putative mechanisms of interleukin (IL)-13 after intestinal I/R injury in the mouse. METHODS: Mouse warm intestinal I/R injury induced by clamping the superior mesenteric artery for 100 min with tissue analysis at 4 and 24 hr after reperfusion. Treated animals received intravenous recombinant murine IL-13 (rIL-13) and anti-IL-13 antibody, whereas controls received saline. RESULTS: rIL-13 administration markedly prolonged animal survival (100% vs. 50% in saline controls) and resulted in near normal histopathological architecture. rIL-13 treatment also significantly decreased myeloperoxidase activity. Mice conditioned with rIL-13 had a markedly depressed Toll-like receptor-4 expression and increased the expression of Stat6, antioxidant hemeoxygenase-1, and antiapoptotic A20, Bcl-2/Bcl-xl, compared with that of controls. Unlike in controls, the expression of mRNA coding for IL-2/interferon-γ, and interferon-γ-inducible protein (IP)-10/monocyte chemotactic protein-1 remained depressed, whereas that of IL-13/IL-4 reciprocally increased in the mice treated with rIL-13. Administration of anti-IL13 antibody alone or in combination with rIL-13 resulted in outcomes similar to that seen in controls. CONCLUSIONS: This study demonstrates for the first time that IL-13 plays a protective role in intestinal warm I/R injury and a critical role in the regulation of Stat6 and Toll-like receptor-4 signaling. The administration of IL-13 exerts cytoprotective effects in this model by regulating innate and adaptive immunity while the removal of IL-13 using antibody therapy abrogates this effect. |
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Authors:
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Douglas G Farmer; Bibo Ke; Xiu-Da Shen; Fady M Kaldas; Feng Gao; Melissa J Watson; Ronald W Busuttil; Jerzy W Kupiec-Weglinski |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Transplantation Volume: 91 ISSN: 1534-6080 ISO Abbreviation: Transplantation Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-25 Completed Date: 2011-06-01 Revised Date: 2012-01-18 |
Medline Journal Info:
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Nlm Unique ID: 0132144 Medline TA: Transplantation Country: United States |
Other Details:
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Languages: eng Pagination: 737-43 Citation Subset: IM |
Affiliation:
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Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplant Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. dgfarmer@mednet.ucla.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptive Immunity* Animals Cytoprotection Immunity, Innate* Interleukin-13 / blood, pharmacology* Intestines / blood supply* Male Mice Mice, Inbred C57BL Peroxidase / metabolism Recombinant Proteins / pharmacology Reperfusion Injury / prevention & control* STAT6 Transcription Factor / physiology Toll-Like Receptor 4 / physiology |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK062357-09/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-13; 0/Recombinant Proteins; 0/STAT6 Transcription Factor; 0/Stat6 protein, mouse; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 4; EC 1.11.1.7/Peroxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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