| Th2 cytokine-induced alterations in intestinal smooth muscle function depend on alternatively activated macrophages. | |
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MedLine Citation:
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PMID: 18471439 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND & AIMS: Enteric nematode infection induces a strong type 2 T helper cell (Th2) cytokine response characterized by increased infiltration of various immune cells, including macrophages. The role of these immune cells in host defense against nematode infection remains poorly defined. The present study investigated the role of macrophages and the arginase pathway in nematode-induced changes in intestinal smooth muscle function and worm expulsion. METHODS: Mice were infected with Nippostrongylus brasiliensis and treated with clodronate-containing liposome to deplete macrophages or given S-(2-boronoethyl)-I-cysteine in drinking water to inhibit arginase activity. Segments of intestinal smooth muscle were suspended in organ baths to determine responses to acetylcholine, 5-hydroxytryptamine, or nerve stimulation. The phenotype of macrophages was monitored by measuring mRNA expression of the specific molecular markers by real-time polymerase chain reaction or viewed by immunofluorescence staining. RESULTS: Infection increased the infiltration of macrophages and up-regulation alternatively activated macrophage markers by a mechanism dependent on interleukin-4 (IL-4) or interleukin-13 (IL-13) activation of signal transducer and activator of transcription 6. Elimination of alternatively activated macrophages blocked smooth muscle hypercontractility and the increased smooth muscle thickness, and impaired worm expulsion. In addition, specific inhibition of arginase activity interfered with smooth muscle contractility, but only partially affected the protective immunity of the host. CONCLUSIONS: These data show that the phenotype of macrophages is determined by the local immune environment and that alternatively activated macrophages play a major role in the effects of Th2 cytokines, IL-4 and IL-13, on intestinal smooth muscle function. |
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Authors:
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Aiping Zhao; Joseph F Urban; Robert M Anthony; Rex Sun; Jennifer Stiltz; Nico van Rooijen; Thomas A Wynn; William C Gause; Terez Shea-Donohue |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2008-04-04 |
Journal Detail:
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Title: Gastroenterology Volume: 135 ISSN: 1528-0012 ISO Abbreviation: Gastroenterology Publication Date: 2008 Jul |
Date Detail:
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Created Date: 2008-07-08 Completed Date: 2008-08-08 Revised Date: 2011-10-12 |
Medline Journal Info:
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Nlm Unique ID: 0374630 Medline TA: Gastroenterology Country: United States |
Other Details:
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Languages: eng Pagination: 217-225.e1 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine and the Mucosal Biology Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arginase / metabolism Female Interleukin-13 / metabolism Interleukin-4 / metabolism Intestines / immunology*, parasitology Macrophages / immunology*, parasitology Mice Mice, Inbred BALB C Mice, Mutant Strains Mice, SCID Muscle, Smooth / immunology*, parasitology Nippostrongylus* Strongylida Infections / immunology* Th2 Cells / immunology*, metabolism, parasitology Up-Regulation / immunology |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI031678-12/AI/NIAID NIH HHS; R01 AI031678-13/AI/NIAID NIH HHS; R01 AI031678-14/AI/NIAID NIH HHS; R01 AI049316-07/AI/NIAID NIH HHS; R01 AI049316-10/AI/NIAID NIH HHS; R01-AI/DK49316/AI/NIAID NIH HHS; R01-AI031678/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-13; 207137-56-2/Interleukin-4; EC 3.5.3.1/Arginase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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