Immunoregulatory mechanisms of macrophage PPAR γ in mice with experimental inflammatory bowel disease
Identifieur interne : 000891 ( Main/Exploration ); précédent : 000890; suivant : 000892Immunoregulatory mechanisms of macrophage PPAR γ in mice with experimental inflammatory bowel disease
Auteurs : Raquel Hontecillas ; William T. Horne ; Montse Climent ; Amir J. Guri ; C. Evans ; Y. Zhang ; Bruno W. Sobral ; Josep Bassaganya-RieraSource :
- Mucosal immunology [ 1933-0219 ] ; 2010.
English descriptors
- KwdEn :
- Animals, Anti-Inflammatory Agents (pharmacology), Anti-Inflammatory Agents (therapeutic use), Cells, Cultured, Colitis (chemically induced), Colitis (drug therapy), Colitis (immunology), Colon (pathology), Computational Biology, Dextran Sulfate (administration & dosage), Disease Models, Animal, Gene Expression Regulation (immunology), Humans, Immunomodulation, Inflammatory Bowel Diseases (drug therapy), Inflammatory Bowel Diseases (immunology), Macrophages (drug effects), Macrophages (immunology), Macrophages (metabolism), Macrophages (pathology), Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Microarray Analysis, Mucous Membrane (pathology), PPAR gamma (antagonists & inhibitors), PPAR gamma (genetics), PPAR gamma (immunology), PPAR gamma (metabolism), T-Lymphocyte Subsets (drug effects), T-Lymphocyte Subsets (immunology), T-Lymphocyte Subsets (metabolism), T-Lymphocyte Subsets (pathology), T-Lymphocytes, Regulatory (drug effects), T-Lymphocytes, Regulatory (immunology), T-Lymphocytes, Regulatory (metabolism), T-Lymphocytes, Regulatory (pathology), Thiazolidinediones (pharmacology), Thiazolidinediones (therapeutic use).
- MESH :
- chemical , administration & dosage : Dextran Sulfate.
- chemical , antagonists & inhibitors : PPAR gamma.
- chemical , genetics : PPAR gamma.
- chemical , immunology : PPAR gamma.
- chemical , metabolism : PPAR gamma.
- chemical , pharmacology : Anti-Inflammatory Agents, Thiazolidinediones.
- chemical , therapeutic use : Anti-Inflammatory Agents, Thiazolidinediones.
- chemically induced : Colitis.
- drug effects : Macrophages, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory.
- drug therapy : Colitis, Inflammatory Bowel Diseases.
- immunology : Colitis, Gene Expression Regulation, Inflammatory Bowel Diseases, Macrophages, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory.
- metabolism : Macrophages, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory.
- pathology : Colon, Macrophages, Mucous Membrane, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory.
- Animals, Cells, Cultured, Computational Biology, Disease Models, Animal, Humans, Immunomodulation, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Microarray Analysis.
Abstract
Peroxisome proliferator-activated receptor γ (PPAR γ) is widely expressed in macrophages and has been identified as a putative target for the development of novel therapies against inflammatory bowel disease (IBD). Computational simulations identified macrophages as key targets for therapeutic interventions against IBD. This study aimed to characterize the mechanisms underlying the beneficial effects of macrophage PPAR γ in IBD. Macrophage-specific PPAR γ deletion significantly exacerbated clinical activity and colonic pathology, impaired the splenic and mesenteric lymph node regulatory T cell compartment, increased percentages of LP CD8+ T cells, increased surface expression of CD40, Ly6C, and TLR-4 in LP macrophages, and upregulated expression of colonic IFN-γ, CXCL9, CXCL10, IL-22, IL1RL1, CCR1, suppressor of cytokine signaling 3 and MCH class II in mice with IBD. Moreover, macrophage PPAR γ was required for accelerating pioglitazone-mediated recovery from DSS colitis, providing a cellular target for the anti-inflammatory effects of PPAR γ agonists in IBD.
Url:
DOI: 10.1038/mi.2010.75
PubMed: 21068720
PubMed Central: 3049196
Affiliations:
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Le document en format XML
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Zhang</name></author><author><name sortKey="Sobral, Bruno W" sort="Sobral, Bruno W" uniqKey="Sobral B" first="Bruno W." last="Sobral">Bruno W. Sobral</name></author><author><name sortKey="Bassaganya Riera, Josep" sort="Bassaganya Riera, Josep" uniqKey="Bassaganya Riera J" first="Josep" last="Bassaganya-Riera">Josep Bassaganya-Riera</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21068720</idno><idno type="pmc">3049196</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049196</idno><idno type="RBID">PMC:3049196</idno><idno type="doi">10.1038/mi.2010.75</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000678</idno><idno type="wicri:Area/Pmc/Curation">000678</idno><idno type="wicri:Area/Pmc/Checkpoint">000576</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">000047</idno><idno type="wicri:Area/PubMed/Curation">000047</idno><idno type="wicri:Area/PubMed/Checkpoint">000047</idno><idno type="wicri:Area/Ncbi/Merge">000176</idno><idno type="wicri:Area/Ncbi/Curation">000176</idno><idno type="wicri:Area/Ncbi/Checkpoint">000176</idno><idno type="wicri:doubleKey">1933-0219:2010:Hontecillas R:immunoregulatory:mechanisms:of</idno><idno type="wicri:Area/Main/Merge">000894</idno><idno type="wicri:Area/Main/Curation">000891</idno><idno type="wicri:Area/Main/Exploration">000891</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Immunoregulatory mechanisms of macrophage PPAR γ in mice with experimental inflammatory bowel disease</title><author><name sortKey="Hontecillas, Raquel" sort="Hontecillas, Raquel" uniqKey="Hontecillas R" first="Raquel" last="Hontecillas">Raquel Hontecillas</name></author><author><name sortKey="Horne, William T" sort="Horne, William T" uniqKey="Horne W" first="William T." last="Horne">William T. Horne</name></author><author><name sortKey="Climent, Montse" sort="Climent, Montse" uniqKey="Climent M" first="Montse" last="Climent">Montse Climent</name></author><author><name sortKey="Guri, Amir J" sort="Guri, Amir J" uniqKey="Guri A" first="Amir J." last="Guri">Amir J. Guri</name></author><author><name sortKey="Evans, C" sort="Evans, C" uniqKey="Evans C" first="C." last="Evans">C. Evans</name></author><author><name sortKey="Zhang, Y" sort="Zhang, Y" uniqKey="Zhang Y" first="Y." last="Zhang">Y. Zhang</name></author><author><name sortKey="Sobral, Bruno W" sort="Sobral, Bruno W" uniqKey="Sobral B" first="Bruno W." last="Sobral">Bruno W. Sobral</name></author><author><name sortKey="Bassaganya Riera, Josep" sort="Bassaganya Riera, Josep" uniqKey="Bassaganya Riera J" first="Josep" last="Bassaganya-Riera">Josep Bassaganya-Riera</name></author></analytic><series><title level="j">Mucosal immunology</title><idno type="ISSN">1933-0219</idno><idno type="eISSN">1935-3456</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Anti-Inflammatory Agents (pharmacology)</term><term>Anti-Inflammatory Agents (therapeutic use)</term><term>Cells, Cultured</term><term>Colitis (chemically induced)</term><term>Colitis (drug therapy)</term><term>Colitis (immunology)</term><term>Colon (pathology)</term><term>Computational Biology</term><term>Dextran Sulfate (administration & dosage)</term><term>Disease Models, Animal</term><term>Gene Expression Regulation (immunology)</term><term>Humans</term><term>Immunomodulation</term><term>Inflammatory Bowel Diseases (drug therapy)</term><term>Inflammatory Bowel Diseases (immunology)</term><term>Macrophages (drug effects)</term><term>Macrophages (immunology)</term><term>Macrophages (metabolism)</term><term>Macrophages (pathology)</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Mutant Strains</term><term>Microarray Analysis</term><term>Mucous Membrane (pathology)</term><term>PPAR gamma (antagonists & inhibitors)</term><term>PPAR gamma (genetics)</term><term>PPAR gamma (immunology)</term><term>PPAR gamma (metabolism)</term><term>T-Lymphocyte Subsets (drug effects)</term><term>T-Lymphocyte Subsets (immunology)</term><term>T-Lymphocyte Subsets (metabolism)</term><term>T-Lymphocyte Subsets (pathology)</term><term>T-Lymphocytes, Regulatory (drug effects)</term><term>T-Lymphocytes, Regulatory (immunology)</term><term>T-Lymphocytes, Regulatory (metabolism)</term><term>T-Lymphocytes, Regulatory (pathology)</term><term>Thiazolidinediones (pharmacology)</term><term>Thiazolidinediones (therapeutic use)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Dextran Sulfate</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>PPAR gamma</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>PPAR gamma</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>PPAR gamma</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>PPAR gamma</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Anti-Inflammatory Agents</term><term>Thiazolidinediones</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Anti-Inflammatory Agents</term><term>Thiazolidinediones</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Colitis</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Macrophages</term><term>T-Lymphocyte Subsets</term><term>T-Lymphocytes, Regulatory</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Colitis</term><term>Inflammatory Bowel Diseases</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Colitis</term><term>Gene Expression Regulation</term><term>Inflammatory Bowel Diseases</term><term>Macrophages</term><term>T-Lymphocyte Subsets</term><term>T-Lymphocytes, Regulatory</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Macrophages</term><term>T-Lymphocyte Subsets</term><term>T-Lymphocytes, Regulatory</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Colon</term><term>Macrophages</term><term>Mucous Membrane</term><term>T-Lymphocyte Subsets</term><term>T-Lymphocytes, Regulatory</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cells, Cultured</term><term>Computational Biology</term><term>Disease Models, Animal</term><term>Humans</term><term>Immunomodulation</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Mutant Strains</term><term>Microarray Analysis</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Peroxisome proliferator-activated receptor γ (PPAR γ) is widely expressed in macrophages and has been identified as a putative target for the development of novel therapies against inflammatory bowel disease (IBD). Computational simulations identified macrophages as key targets for therapeutic interventions against IBD. This study aimed to characterize the mechanisms underlying the beneficial effects of macrophage PPAR γ in IBD. Macrophage-specific PPAR γ deletion significantly exacerbated clinical activity and colonic pathology, impaired the splenic and mesenteric lymph node regulatory T cell compartment, increased percentages of LP CD8+ T cells, increased surface expression of CD40, Ly6C, and TLR-4 in LP macrophages, and upregulated expression of colonic IFN-γ, CXCL9, CXCL10, IL-22, IL1RL1, CCR1, suppressor of cytokine signaling 3 and MCH class II in mice with IBD. Moreover, macrophage PPAR γ was required for accelerating pioglitazone-mediated recovery from DSS colitis, providing a cellular target for the anti-inflammatory effects of PPAR γ agonists in IBD.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Hanauer, Sb" uniqKey="Hanauer S">SB Hanauer</name></author><author><name sortKey="Present, Dh" uniqKey="Present D">DH Present</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassaganya Riera, J" uniqKey="Bassaganya Riera J">J Bassaganya-Riera</name></author><author><name sortKey="Reynolds, K" uniqKey="Reynolds K">K Reynolds</name></author><author><name sortKey="Martino Catt, S" uniqKey="Martino Catt S">S Martino-Catt</name></author><author><name sortKey="Cui, Y" uniqKey="Cui Y">Y Cui</name></author><author><name sortKey="Hennighausen, L" uniqKey="Hennighausen L">L Hennighausen</name></author><author><name sortKey="Gonzalez, F" uniqKey="Gonzalez F">F 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Evans</name><name sortKey="Guri, Amir J" sort="Guri, Amir J" uniqKey="Guri A" first="Amir J." last="Guri">Amir J. Guri</name><name sortKey="Hontecillas, Raquel" sort="Hontecillas, Raquel" uniqKey="Hontecillas R" first="Raquel" last="Hontecillas">Raquel Hontecillas</name><name sortKey="Horne, William T" sort="Horne, William T" uniqKey="Horne W" first="William T." last="Horne">William T. Horne</name><name sortKey="Sobral, Bruno W" sort="Sobral, Bruno W" uniqKey="Sobral B" first="Bruno W." last="Sobral">Bruno W. Sobral</name><name sortKey="Zhang, Y" sort="Zhang, Y" uniqKey="Zhang Y" first="Y." last="Zhang">Y. Zhang</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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