| Toll-like receptor 4 is protective against neonatal murine ischemia-reperfusion intestinal injury. | |
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MedLine Citation:
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PMID: 20620328 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Premature infants receiving probiotics have a decreased incidence of necrotizing enterocolitis. This may be mediated by intestinal bacterial signaling via toll-like receptors (TLRs) 2 and 4 maintaining intestinal homeostasis. We hypothesized that TLRs 2 and 4 are protective against ischemia-reperfusion (I/R) intestinal injury. METHODS: Two-week-old C57BL/6 wild-type (WT), B6.TLR2(-/-), B6.TLR4(-/-), B6.TLR2(-/-)4(-/-), and microbially reduced (antibiotic-treated) mice (MR) underwent 60 minutes of superior mesenteric artery occlusion (I) followed by 90 minutes of reperfusion (R). Small intestine was harvested for analysis of microscopic injury, apoptosis, and inflammatory gene expression using quantitative polymerase chain reaction. RESULTS: After I/R, the median histologic injury scores of the B6.TLR4(-/-), B6.TLR2(-/-)4(-/-), and MR pups were higher than the WT or B6.TLR2(-/-) pups that corresponded with greater apoptosis based on terminal deoxynucleotidyl transferase-mediated dUTP-FITC nick-end labeling and activated caspase-3 immunostaining. B6.TLR4(-/-), B6.TLR2(-/-)4(-/-), and MR also had elevated tissue innate immunity-associated chemokine and cytokine expression. CONCLUSIONS: Neonatal mice deficient in TLR4, either alone or also deficient in TLR2, as well as those lacking a normal commensal intestinal microbiome are more susceptible to an I/R model of intestinal injury. These results may provide a mechanism for commensal bacterial-mediated protection, which may help to direct further studies to elucidate the mechanism of probiotic protection. |
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Authors:
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Philip M Tatum; Carroll M Harmon; Robin G Lorenz; Reed A Dimmitt |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of pediatric surgery Volume: 45 ISSN: 1531-5037 ISO Abbreviation: J. Pediatr. Surg. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-07-12 Completed Date: 2010-10-21 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0052631 Medline TA: J Pediatr Surg Country: United States |
Other Details:
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Languages: eng Pagination: 1246-55 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35233, USA. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Apoptosis Caspase 3 / metabolism Enterocolitis, Necrotizing / genetics, immunology, prevention & control* Female Gene Expression Regulation, Developmental* Immunity, Innate* In Situ Nick-End Labeling Intestine, Small / blood supply, immunology, metabolism* Mice Mice, Inbred C57BL Polymerase Chain Reaction RNA / genetics* Reperfusion Injury / genetics, immunology, prevention & control* Toll-Like Receptor 2 / biosynthesis, genetics Toll-Like Receptor 4 / biosynthesis, genetics* |
| Grant Support | |
ID/Acronym/Agency:
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C06RR020136/RR/NCRR NIH HHS; K08 HD046506-05/HD/NICHD NIH HHS; K08 HD46506/HD/NICHD NIH HHS; P01 DK071176/DK/NIDDK NIH HHS; P01 DK071176-03/DK/NIDDK NIH HHS; P30 DK064400/DK/NIDDK NIH HHS; R01 DK059911/DK/NIDDK NIH HHS; R01 DK059911-05/DK/NIDDK NIH HHS; R24 DK064400-09/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Toll-Like Receptor 2; 0/Toll-Like Receptor 4; 63231-63-0/RNA; EC 3.4.22.-/Caspase 3 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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