Immunoregulatory mechanisms of macrophage PPAR γ in mice with experimental inflammatory bowel disease
Identifieur interne : 000576 ( Pmc/Checkpoint ); précédent : 000575; suivant : 000577Immunoregulatory 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.
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:
Links toward previous steps (curation, corpus...)
Links to Exploration step
PMC:3049196Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">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></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></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></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 Gonzalez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Desreumaux, P" uniqKey="Desreumaux P">P Desreumaux</name></author><author><name sortKey="Dubuquoy, L" uniqKey="Dubuquoy L">L Dubuquoy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lewis, Jd" uniqKey="Lewis J">JD Lewis</name></author><author><name sortKey="Lichtenstein, Gr" uniqKey="Lichtenstein G">GR Lichtenstein</name></author><author><name sortKey="Deren, Jj" uniqKey="Deren J">JJ Deren</name></author><author><name sortKey="Sands, Be" uniqKey="Sands B">BE Sands</name></author><author><name sortKey="Hanauer, Sb" uniqKey="Hanauer S">SB Hanauer</name></author><author><name sortKey="Katz, Ja" uniqKey="Katz J">JA Katz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marcy, Tr" uniqKey="Marcy T">TR Marcy</name></author><author><name sortKey="Britton, Ml" uniqKey="Britton M">ML Britton</name></author><author><name sortKey="Blevins, Sm" uniqKey="Blevins S">SM Blevins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Desvergne, B" uniqKey="Desvergne B">B Desvergne</name></author><author><name sortKey="Wahli, W" uniqKey="Wahli W">W Wahli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassaganya Riera, J" uniqKey="Bassaganya Riera J">J Bassaganya-Riera</name></author><author><name sortKey="Pogranichniy, Rm" uniqKey="Pogranichniy R">RM Pogranichniy</name></author><author><name sortKey="Jobgen, Sc" uniqKey="Jobgen S">SC Jobgen</name></author><author><name sortKey="Halbur, Pg" uniqKey="Halbur P">PG Halbur</name></author><author><name sortKey="Yoon, Kj" uniqKey="Yoon K">KJ Yoon</name></author><author><name sortKey="O Shea, M" uniqKey="O Shea M">M O'Shea</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guri, Aj" uniqKey="Guri A">AJ Guri</name></author><author><name sortKey="Hontecillas, R" uniqKey="Hontecillas R">R Hontecillas</name></author><author><name sortKey="Bassaganya Riera, J" uniqKey="Bassaganya Riera J">J Bassaganya-Riera</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guri, Aj" uniqKey="Guri A">AJ Guri</name></author><author><name sortKey="Evans, Np" uniqKey="Evans N">NP Evans</name></author><author><name sortKey="Hontecillas, R" uniqKey="Hontecillas R">R Hontecillas</name></author><author><name sortKey="Bassaganya Riera, J" uniqKey="Bassaganya Riera J">J Bassaganya-Riera</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hontecillas, R" uniqKey="Hontecillas R">R Hontecillas</name></author><author><name sortKey="Wannemeulher, Mj" uniqKey="Wannemeulher M">MJ Wannemeulher</name></author><author><name sortKey="Zimmerman, Dr" uniqKey="Zimmerman D">DR Zimmerman</name></author><author><name sortKey="Hutto, Dl" uniqKey="Hutto D">DL Hutto</name></author><author><name sortKey="Wilson, Jh" uniqKey="Wilson J">JH Wilson</name></author><author><name sortKey="Ahn, Du" uniqKey="Ahn D">DU Ahn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassaganya Riera, J" uniqKey="Bassaganya Riera J">J Bassaganya-Riera</name></author><author><name sortKey="Hontecillas, R" uniqKey="Hontecillas R">R Hontecillas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hontecillas, R" uniqKey="Hontecillas R">R Hontecillas</name></author><author><name sortKey="Bassaganya Riera, J" uniqKey="Bassaganya Riera J">J Bassaganya-Riera</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Evans, Np" uniqKey="Evans N">NP Evans</name></author><author><name sortKey="Misyak, Sa" uniqKey="Misyak S">SA Misyak</name></author><author><name sortKey="Schmelz, Em" uniqKey="Schmelz E">EM Schmelz</name></author><author><name sortKey="Guri, Aj" uniqKey="Guri A">AJ Guri</name></author><author><name sortKey="Hontecillas, R" uniqKey="Hontecillas R">R Hontecillas</name></author><author><name sortKey="Bassaganya Riera, J" uniqKey="Bassaganya Riera J">J Bassaganya-Riera</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guri, Aj" uniqKey="Guri A">AJ Guri</name></author><author><name sortKey="Mohapatra, Sk" uniqKey="Mohapatra S">SK Mohapatra</name></author><author><name sortKey="Horne, Wt" uniqKey="Horne W">WT Horne</name></author><author><name sortKey="Hontecillas, R" uniqKey="Hontecillas R">R Hontecillas</name></author><author><name sortKey="Bassaganya Riera, J" uniqKey="Bassaganya Riera J">J Bassaganya-Riera</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adachi, M" uniqKey="Adachi M">M Adachi</name></author><author><name sortKey="Kurotani, R" uniqKey="Kurotani R">R Kurotani</name></author><author><name sortKey="Morimura, K" uniqKey="Morimura K">K Morimura</name></author><author><name sortKey="Shah, Y" uniqKey="Shah Y">Y Shah</name></author><author><name sortKey="Sanford, M" uniqKey="Sanford M">M Sanford</name></author><author><name sortKey="Madison, Bb" uniqKey="Madison B">BB Madison</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mohapatra, Sk" uniqKey="Mohapatra S">SK Mohapatra</name></author><author><name sortKey="Guri, Aj" uniqKey="Guri A">AJ Guri</name></author><author><name sortKey="Climent, M" uniqKey="Climent M">M Climent</name></author><author><name sortKey="Vives, C" uniqKey="Vives C">C Vives</name></author><author><name sortKey="Carbo, A" uniqKey="Carbo A">A Carbo</name></author><author><name sortKey="Horne, Wt" uniqKey="Horne W">WT Horne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wendelsdorf, K" uniqKey="Wendelsdorf K">K Wendelsdorf</name></author><author><name sortKey="Bassaganya Riera, J" uniqKey="Bassaganya Riera J">J Bassaganya-Riera</name></author><author><name sortKey="Hontecillas, R" uniqKey="Hontecillas R">R Hontecillas</name></author><author><name sortKey="Eubank, S" uniqKey="Eubank S">S Eubank</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shah, Ym" uniqKey="Shah Y">YM Shah</name></author><author><name sortKey="Morimura, K" uniqKey="Morimura K">K Morimura</name></author><author><name sortKey="Gonzalez, Fj" uniqKey="Gonzalez F">FJ Gonzalez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boismenu, R" uniqKey="Boismenu R">R Boismenu</name></author><author><name sortKey="Havran, Wl" uniqKey="Havran W">WL Havran</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassaganya Riera, J" uniqKey="Bassaganya Riera J">J Bassaganya-Riera</name></author><author><name sortKey="Hontecillas, R" uniqKey="Hontecillas R">R Hontecillas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vowinkel, T" uniqKey="Vowinkel T">T Vowinkel</name></author><author><name sortKey="Anthoni, C" uniqKey="Anthoni C">C Anthoni</name></author><author><name sortKey="Wood, Kc" uniqKey="Wood K">KC Wood</name></author><author><name sortKey="Stokes, Ky" uniqKey="Stokes K">KY Stokes</name></author><author><name sortKey="Russell, J" uniqKey="Russell J">J Russell</name></author><author><name sortKey="Gray, L" uniqKey="Gray L">L Gray</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lapaque, N" uniqKey="Lapaque N">N Lapaque</name></author><author><name sortKey="Takeuchi, O" uniqKey="Takeuchi O">O Takeuchi</name></author><author><name sortKey="Corrales, F" uniqKey="Corrales F">F Corrales</name></author><author><name sortKey="Akira, S" uniqKey="Akira S">S Akira</name></author><author><name sortKey="Moriyon, I" uniqKey="Moriyon I">I Moriyon</name></author><author><name sortKey="Howard, Jc" uniqKey="Howard J">JC Howard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dubuquoy, L" uniqKey="Dubuquoy L">L Dubuquoy</name></author><author><name sortKey="Jansson, Ee" uniqKey="Jansson E">EE Jansson</name></author><author><name sortKey="Deeb, S" uniqKey="Deeb S">S Deeb</name></author><author><name sortKey="Rakotobe, S" uniqKey="Rakotobe S">S Rakotobe</name></author><author><name sortKey="Karoui, M" uniqKey="Karoui M">M Karoui</name></author><author><name sortKey="Colombel, Jf" uniqKey="Colombel J">JF Colombel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Odegaard, Ji" uniqKey="Odegaard J">JI Odegaard</name></author><author><name sortKey="Ricardo Gonzalez, Rr" uniqKey="Ricardo Gonzalez R">RR Ricardo-Gonzalez</name></author><author><name sortKey="Goforth, Mh" uniqKey="Goforth M">MH Goforth</name></author><author><name sortKey="Morel, Cr" uniqKey="Morel C">CR Morel</name></author><author><name sortKey="Subramanian, V" uniqKey="Subramanian V">V Subramanian</name></author><author><name sortKey="Mukundan, L" uniqKey="Mukundan L">L Mukundan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pascual, G" uniqKey="Pascual G">G Pascual</name></author><author><name sortKey="Fong, Al" uniqKey="Fong A">AL Fong</name></author><author><name sortKey="Ogawa, S" uniqKey="Ogawa S">S Ogawa</name></author><author><name sortKey="Gamliel, A" uniqKey="Gamliel A">A Gamliel</name></author><author><name sortKey="Li, Ac" uniqKey="Li A">AC Li</name></author><author><name sortKey="Perissi, V" uniqKey="Perissi V">V Perissi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ricote, M" uniqKey="Ricote M">M Ricote</name></author><author><name sortKey="Huang, J" uniqKey="Huang J">J Huang</name></author><author><name sortKey="Fajas, L" uniqKey="Fajas L">L Fajas</name></author><author><name sortKey="Li, A" uniqKey="Li A">A Li</name></author><author><name sortKey="Welch, J" uniqKey="Welch J">J Welch</name></author><author><name sortKey="Najib, J" uniqKey="Najib J">J Najib</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ricote, M" uniqKey="Ricote M">M Ricote</name></author><author><name sortKey="Li, Ac" uniqKey="Li A">AC Li</name></author><author><name sortKey="Willson, Tm" uniqKey="Willson T">TM Willson</name></author><author><name sortKey="Kelly, Cj" uniqKey="Kelly C">CJ Kelly</name></author><author><name sortKey="Glass, Ck" uniqKey="Glass C">CK Glass</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lewis, Jd" uniqKey="Lewis J">JD Lewis</name></author><author><name sortKey="Lichtenstein, Gr" uniqKey="Lichtenstein G">GR Lichtenstein</name></author><author><name sortKey="Stein, Rb" uniqKey="Stein R">RB Stein</name></author><author><name sortKey="Deren, Jj" uniqKey="Deren J">JJ Deren</name></author><author><name sortKey="Judge, Ta" uniqKey="Judge T">TA Judge</name></author><author><name sortKey="Fogt, F" uniqKey="Fogt F">F Fogt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sun, H" uniqKey="Sun H">H Sun</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y Huang</name></author><author><name sortKey="Yu, X" uniqKey="Yu X">X Yu</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author><author><name sortKey="Yang, J" uniqKey="Yang J">J Yang</name></author><author><name sortKey="Li, R" uniqKey="Li R">R Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hu, Q" uniqKey="Hu Q">Q Hu</name></author><author><name sortKey="Zhang, Xj" uniqKey="Zhang X">XJ Zhang</name></author><author><name sortKey="Zhang, C" uniqKey="Zhang C">C Zhang</name></author><author><name sortKey="Zhao, Yx" uniqKey="Zhao Y">YX Zhao</name></author><author><name sortKey="He, H" uniqKey="He H">H He</name></author><author><name sortKey="Liu, Cx" uniqKey="Liu C">CX Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, Yj" uniqKey="Zhang Y">YJ Zhang</name></author><author><name sortKey="Yang, X" uniqKey="Yang X">X Yang</name></author><author><name sortKey="Kong, Qy" uniqKey="Kong Q">QY Kong</name></author><author><name sortKey="Zhang, Yf" uniqKey="Zhang Y">YF Zhang</name></author><author><name sortKey="Chen, Wy" uniqKey="Chen W">WY Chen</name></author><author><name sortKey="Dong, Xq" uniqKey="Dong X">XQ Dong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, Z" uniqKey="Liu Z">Z Liu</name></author><author><name sortKey="Colpaert, S" uniqKey="Colpaert S">S Colpaert</name></author><author><name sortKey="D Haens, Gr" uniqKey="D Haens G">GR D'Haens</name></author><author><name sortKey="Kasran, A" uniqKey="Kasran A">A Kasran</name></author><author><name sortKey="De Boer, M" uniqKey="De Boer M">M de Boer</name></author><author><name sortKey="Rutgeerts, P" uniqKey="Rutgeerts P">P Rutgeerts</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Battaglia, E" uniqKey="Battaglia E">E Battaglia</name></author><author><name sortKey="Biancone, L" uniqKey="Biancone L">L Biancone</name></author><author><name sortKey="Resegotti, A" uniqKey="Resegotti A">A Resegotti</name></author><author><name sortKey="Emanuelli, G" uniqKey="Emanuelli G">G Emanuelli</name></author><author><name sortKey="Fronda, Gr" uniqKey="Fronda G">GR Fronda</name></author><author><name sortKey="Camussi, G" uniqKey="Camussi G">G Camussi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Polese, L" uniqKey="Polese L">L Polese</name></author><author><name sortKey="Angriman, I" uniqKey="Angriman I">I Angriman</name></author><author><name sortKey="Cecchetto, A" uniqKey="Cecchetto A">A Cecchetto</name></author><author><name sortKey="Norberto, L" uniqKey="Norberto L">L Norberto</name></author><author><name sortKey="Scarpa, M" uniqKey="Scarpa M">M Scarpa</name></author><author><name sortKey="Ruffolo, C" uniqKey="Ruffolo C">C Ruffolo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carlsen, Hs" uniqKey="Carlsen H">HS Carlsen</name></author><author><name sortKey="Yamanaka, T" uniqKey="Yamanaka T">T Yamanaka</name></author><author><name sortKey="Scott, H" uniqKey="Scott H">H Scott</name></author><author><name sortKey="Rugtveit, J" uniqKey="Rugtveit J">J Rugtveit</name></author><author><name sortKey="Brandtzaeg, P" uniqKey="Brandtzaeg P">P Brandtzaeg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Borcherding, F" uniqKey="Borcherding F">F Borcherding</name></author><author><name sortKey="Nitschke, M" uniqKey="Nitschke M">M Nitschke</name></author><author><name sortKey="Hundorfean, G" uniqKey="Hundorfean G">G Hundorfean</name></author><author><name sortKey="Rupp, J" uniqKey="Rupp J">J Rupp</name></author><author><name sortKey="Von Smolinski, D" uniqKey="Von Smolinski D">D von Smolinski</name></author><author><name sortKey="Bieber, K" uniqKey="Bieber K">K Bieber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matsutani, T" uniqKey="Matsutani T">T Matsutani</name></author><author><name sortKey="Anantha Samy, Ts" uniqKey="Anantha Samy T">TS Anantha Samy</name></author><author><name sortKey="Kang, Sc" uniqKey="Kang S">SC Kang</name></author><author><name sortKey="Bland, Ki" uniqKey="Bland K">KI Bland</name></author><author><name sortKey="Chaudry, Ih" uniqKey="Chaudry I">IH Chaudry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassaganya Riera, J" uniqKey="Bassaganya Riera J">J Bassaganya-Riera</name></author><author><name sortKey="Misyak, S" uniqKey="Misyak S">S Misyak</name></author><author><name sortKey="Guri, Aj" uniqKey="Guri A">AJ Guri</name></author><author><name sortKey="Hontecillas, R" uniqKey="Hontecillas R">R Hontecillas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gautier, L" uniqKey="Gautier L">L Gautier</name></author><author><name sortKey="Cope, L" uniqKey="Cope L">L Cope</name></author><author><name sortKey="Bolstad, Bm" uniqKey="Bolstad B">BM Bolstad</name></author><author><name sortKey="Irizarry, Ra" uniqKey="Irizarry R">RA Irizarry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gentleman, Rc" uniqKey="Gentleman R">RC Gentleman</name></author><author><name sortKey="Carey, Vj" uniqKey="Carey V">VJ Carey</name></author><author><name sortKey="Bates, Dm" uniqKey="Bates D">DM Bates</name></author><author><name sortKey="Bolstad, B" uniqKey="Bolstad B">B Bolstad</name></author><author><name sortKey="Dettling, M" uniqKey="Dettling M">M Dettling</name></author><author><name sortKey="Dudoit, S" uniqKey="Dudoit S">S Dudoit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Willems, F" uniqKey="Willems F">F Willems</name></author><author><name sortKey="Vollstedt, S" uniqKey="Vollstedt S">S Vollstedt</name></author><author><name sortKey="Suter, M" uniqKey="Suter M">M Suter</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101299742</journal-id><journal-id journal-id-type="pubmed-jr-id">35518</journal-id><journal-id journal-id-type="nlm-ta">Mucosal Immunol</journal-id><journal-id journal-id-type="iso-abbrev">Mucosal Immunol</journal-id><journal-title-group><journal-title>Mucosal immunology</journal-title></journal-title-group><issn pub-type="ppub">1933-0219</issn><issn pub-type="epub">1935-3456</issn></journal-meta><article-meta><article-id pub-id-type="pmid">21068720</article-id><article-id pub-id-type="pmc">3049196</article-id><article-id pub-id-type="doi">10.1038/mi.2010.75</article-id><article-id pub-id-type="manuscript">NIHMS253584</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Immunoregulatory mechanisms of macrophage PPAR γ in mice with experimental inflammatory bowel disease</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Hontecillas</surname><given-names>Raquel</given-names></name></contrib><contrib contrib-type="author"><name><surname>Horne</surname><given-names>William T.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Climent</surname><given-names>Montse</given-names></name></contrib><contrib contrib-type="author"><name><surname>Guri</surname><given-names>Amir J.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Evans</surname><given-names>C.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Y.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Sobral</surname><given-names>Bruno W.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Bassaganya-Riera</surname><given-names>Josep</given-names></name></contrib><aff id="A1">Nutritional Immunology and Molecular Medicine Laboratory, CyberInfrastructure Division, Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, 24060, United States of America</aff></contrib-group><author-notes><corresp id="cor1"><label>*</label>To whom correspondence should be addressed at: Dr. Josep Bassaganya-Riera, Laboratory of Nutritional Immunology & Molecular Medicine, Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061. Phone: (540) 231-7421, fax: (540) 231-2606, and <email>jbassaga@vt.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>19</day><month>11</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>10</day><month>11</month><year>2010</year></pub-date><pub-date pub-type="ppub"><month>5</month><year>2011</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>11</month><year>2011</year></pub-date><volume>4</volume><issue>3</issue><fpage>304</fpage><lpage>313</lpage><pmc-comment>elocation-id from pubmed: 10.1038/mi.2010.75</pmc-comment>
<permissions><license xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms"><license-p>Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:<ext-link ext-link-type="uri" xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms">http://www.nature.com/authors/editorial_policies/license.html#terms</ext-link></license-p></license></permissions><abstract><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></abstract></article-meta></front><floats-group><fig id="F1" position="float"><label>Figure 1</label><caption><title>Genotyping of PPAR γ flfl; Lysozyme M-Cre+ (LC+) and Lysozyme MCre- (LC−) control mice</title><p id="P38">Conditional deletion of the PPAR γ gene via Lysozyme M-Cre-mediated recombination was examined in mouse tissues by PCR analysis. The flox (fl) allele at 275 bp and the null allele at 400 bp. (A) Left to right: depicts fl/fl in bone marrow-derived macrophages (BMM) without recombination (LC−) (<italic>lane 1</italic>) or with recombination (LC+) (<italic>lane 2</italic>). Homogenized whole spleen, mesenteric lymph node (MLN), and colon without recombination (LC−) (<italic>lanes 3, 5, 7</italic>) or with recombination (LC+) (<italic>lanes 4, 6, 8</italic>). (B) Left to right: depicts PPAR γ (top panel) and β actin (bottom panel) protein expression as measured by Western Blot in BMM and colon of LC− (<italic>lanes</italic> 1 and 3) and LC+ (<italic>lanes</italic> 2 and 4) mice. (C) Quantification of PPAR γ (left panel) and CD36 (right panel) colonic mRNA expression by real-time quantitative RT-PCR in LC− and LC+ mice.</p></caption><graphic xlink:href="nihms253584f1"></graphic></fig><fig id="F2" position="float"><label>Figure 2</label><caption><title>Effect of macrophage-specific PPAR γ deletion on disease severity and macroscopic lesions in spleen and colon of mice with experimental IBD</title><p id="P39">PPAR γ flfl; Lysozyme M-Cre+ and Lysozyme M-Cre− control mice were challenged with 2.5% dextran sodium sulfate (DSS) for 7 days. The disease activity index (DAI), a composite score reflecting clinical sings of the disease was assessed daily (A) and the macroscopic lesions in colon (B) and spleen (C) were determine on day 7. Data are represented as mean ± standard error of groups of 10 mice. Points with an asterisk are significantly different (<italic>P</italic><0.05).</p></caption><graphic xlink:href="nihms253584f2"></graphic></fig><fig id="F3" position="float"><label>Figure 3</label><caption><title>Effect of pioglitazone and macrophage-specific PPAR γ deletion in the clinical recovery from experimental IBD</title><p id="P40">Treatment with the PPAR gamma agonist pioglitazone (PIA) accelerates recovery from gut inflammation in Lysozyme M-Cre− mice but not in macrophage-specific PPAR γ null mice (Lysozyme M-Cre+). Data are represented as mean ± standard error of groups of 10 mice. Means without a common letter superscript are significantly (<italic>P<0.05</italic>) different.</p></caption><graphic xlink:href="nihms253584f3"></graphic></fig><fig id="F4" position="float"><label>Figure 4</label><caption><title>Effect of macrophage-specific PPAR γ deletion on colon histopathology and inflammation of mice with experimental IBD</title><p id="P41">PPAR γ flfl; Lysozyme M-Cre+ and Lysozyme M-Cre− control mice were challenged with 2.5% dextran sodium sulfate (DSS) for 7 days. Representative photomicrographs of colonic samples from LC− (A) and LC+ (B) mice with DSS colitis (Original magnification, 40 ×). Colonic specimens underwent blinded histological examination and were scored (1–4) on epithelial erosion (C), mucosal wall thickening (D), and leukocyte infiltration (E) on day 7 of the challenge. Data are represented as mean ± standard error of groups of 10 mice. Points with an asterisk are significantly different (<italic>P</italic><0.05).</p></caption><graphic xlink:href="nihms253584f4"></graphic></fig><fig id="F5" position="float"><label>Figure 5</label><caption><title>Effect of macrophage-specific PPAR γ deletion on immune cell subsets in blood and spleen from mice with experimental IBD</title><p id="P42">Blood (A–C) and spleen (D–F) from PPAR γ flfl; Lysozyme M-Cre+ and Lysozyme M-Cre− mice were immunophenotyped. Data were collected on day 7 of the dextran sodium sulfate (DSS) challenge and were analyzed with the FACS Diva software. Blood monocytes or spleen T cell subsets were selected by gating first on the viable cells based on FSC and SSC. Monocytes were then gated on F4/80+ CD11b+ and within this cell population, MCP-1 and MHC-II mean fluorescence intensity (MFI) were then examined. Splenocytes were gated on CD3+CD4+ and CD3+CD8+ or CD4+CD25+FOXP3+ to characterize the T cell subsets. Data are represented as mean ± standard error of groups of 10 mice. Points with an asterisk are significantly different (<italic>P</italic><0.05).</p></caption><graphic xlink:href="nihms253584f5"></graphic></fig><fig id="F6" position="float"><label>Figure 6</label><caption><title>Effect of macrophage-specific PPAR γ deletion on immune cell subsets in mesenteric lymph nodes (MLN) from mice with experimental IBD</title><p id="P43">MLN-derived cells from PPAR γ flfl; Lysozyme M-Cre+ and Lysozyme M-Cre− mice were immunophenotyped to identify immune cell subsets by flow cytometry. Data were collected on day 7 of the dextran sodium sulfate (DSS) challenge and were analyzed with the FACS Diva software. MLN macrophages were selected based on F4/80 and CD11b expression in the cell viable gate and then CD40 expression within this population was determined by assessing mean fluorescence activity (MFI). For T-cells, all viable MLN cells were selected using FSC and SSC and the gated on CD3+CD4+ and CD3+CD8+ and CD4+CD25+FOXP3+. Data are represented as mean ± standard error of groups of 10 mice. Points with an asterisk are significantly different (<italic>P</italic><0.05).</p></caption><graphic xlink:href="nihms253584f6"></graphic></fig><fig id="F7" position="float"><label>Figure 7</label><caption><title>Effect of macrophage-specific PPAR γ deletion on immune cell subsets in the colonic lamina propria (LP) from mice with experimental IBD</title><p id="P44">Colonic LP cells from PPAR γ flfl; Lysozyme M-Cre+ and Lysozyme M-Cre− mice were immunophenotyped to identify immune cell subsets by flow cytometry. Data were collected on day 7 of the dextran sodium sulfate (DSS) challenge and were analyzed with the FACS Diva software. LP macrophages were selected based on F4/80 and CD11b expression in the cell viable gate and then CD40, Ly6C and TLR-4 expression within this population was determined by assessing mean fluorescence activity (MFI). For T-cells, all viable MLN cells were selected using FSC and SSC and the gated on CD3+CD4+ and CD3+CD8+. Data are represented as mean ± standard error of groups of 10 mice. Points with an asterisk are significantly different (<italic>P</italic><0.05).</p></caption><graphic xlink:href="nihms253584f7"></graphic></fig><fig id="F8" position="float"><label>Figure 8</label><caption><title>Effect of macrophage-specific PPAR γ deletion on target gene expression in the colonic mucosa of mice with experimental IBD</title><p id="P45">Expression of PPAR γ (A), IL-1β (B) MAdCAM-1 (C), MCP-1 (D), IL-6 (E), IFN-γ (F), ICAM-1 (G), MIP-1α (H) was assessed in colonic mucosal specimens recovered from PPAR γ flfl; Lysozyme M-Cre+ and Lysozyme M-Cre− mice. Data are represented as mean ± standard error of groups of 10 mice. Points with an asterisk are significantly different (<italic>P</italic><0.05).</p></caption><graphic xlink:href="nihms253584f8"></graphic></fig><fig id="F9" position="float"><label>Figure 9</label><caption><title>Effect of macrophage-specific PPAR γ deletion on metabolically active gene expression in the colonic mucosa of mice with experimental IBD</title><p id="P46">Expression of cytochrome P450 (CYP4B1, A) and PPAR α (B) was assessed in colonic mucosal specimens recovered from PPAR γ flfl; Lysozyme M-Cre+ and Lysozyme M-Cre− mice. Data are represented as mean ± standard error of groups of 10 mice. Points with an asterisk are significantly different (<italic>P</italic><0.05).</p></caption><graphic xlink:href="nihms253584f9"></graphic></fig></floats-group></pmc><affiliations><list></list><tree><noCountry><name sortKey="Bassaganya Riera, Josep" sort="Bassaganya Riera, Josep" uniqKey="Bassaganya Riera J" first="Josep" last="Bassaganya-Riera">Josep Bassaganya-Riera</name><name sortKey="Climent, Montse" sort="Climent, Montse" uniqKey="Climent M" first="Montse" last="Climent">Montse Climent</name><name sortKey="Evans, C" sort="Evans, C" uniqKey="Evans C" first="C." last="Evans">C. 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)
EXPLOR_STEP=$WICRI_ROOT/Ticri/CIDE/explor/CyberinfraV1/Data/Pmc/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000576 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd -nk 000576 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Ticri/CIDE
|area= CyberinfraV1
|flux= Pmc
|étape= Checkpoint
|type= RBID
|clé= PMC:3049196
|texte= Immunoregulatory mechanisms of macrophage PPAR γ in mice with experimental inflammatory bowel disease
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/RBID.i -Sk "pubmed:21068720" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd \
| NlmPubMed2Wicri -a CyberinfraV1
| This area was generated with Dilib version V0.6.25. |  |