CETP Lowers TLR4 Expression Which Attenuates the Inflammatory Response Induced by LPS and Polymicrobial Sepsis
Sepsis is a systemic inflammatory response to infection eliciting high mortality rate which is a serious health problem. Despite numerous studies seeking for therapeutic alternatives, the mechanisms involved in this disease remain elusive. In this study we evaluated the influence of cholesteryl este...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/1784014 |
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| author | Tatiana Martins Venancio Roberta Marcondes Machado Angela Castoldi Mariane Tami Amano Valeria Sutti Nunes Eder Carlos Rocha Quintao Niels Olsen Saraiva Camara Francisco Garcia Soriano Patrícia Miralda Cazita |
| author_facet | Tatiana Martins Venancio Roberta Marcondes Machado Angela Castoldi Mariane Tami Amano Valeria Sutti Nunes Eder Carlos Rocha Quintao Niels Olsen Saraiva Camara Francisco Garcia Soriano Patrícia Miralda Cazita |
| author_sort | Tatiana Martins Venancio |
| collection | DOAJ |
| description | Sepsis is a systemic inflammatory response to infection eliciting high mortality rate which is a serious health problem. Despite numerous studies seeking for therapeutic alternatives, the mechanisms involved in this disease remain elusive. In this study we evaluated the influence of cholesteryl ester transfer protein (CETP), a glycoprotein that promotes the transfer of lipids between lipoproteins, on the inflammatory response in mice. Human CETP transgenic mice were compared to control mice (wild type, WT) after polymicrobial sepsis induced by cecal ligation and puncture (CLP), aiming at investigating their survival rate and inflammatory profiles. Macrophages from the peritoneal cavity were stimulated with LPS in the presence or absence of recombinant CETP for phenotypic and functional studies. In comparison to WT mice, CETP mice showed higher survival rate, lower IL-6 plasma concentration, and decreased liver toll-like receptor 4 (TLR4) and acyloxyacyl hydrolase (AOAH) protein. Moreover, macrophages from WT mice to which recombinant human CETP was added decreased LPS uptake, TLR4 expression, NF-κB activation and IL-6 secretion. This raises the possibility for new therapeutic tools in sepsis while suggesting that lowering CETP by pharmacological inhibitors should be inconvenient in the context of sepsis and infectious diseases. |
| format | Article |
| id | doaj-art-90049180dcf5424dbe5cd5b5a9c8ab87 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-90049180dcf5424dbe5cd5b5a9c8ab872025-08-20T03:37:19ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/17840141784014CETP Lowers TLR4 Expression Which Attenuates the Inflammatory Response Induced by LPS and Polymicrobial SepsisTatiana Martins Venancio0Roberta Marcondes Machado1Angela Castoldi2Mariane Tami Amano3Valeria Sutti Nunes4Eder Carlos Rocha Quintao5Niels Olsen Saraiva Camara6Francisco Garcia Soriano7Patrícia Miralda Cazita8Lipids Laboratory (LIM 10), Faculty of Medical Sciences, The University of São Paulo, São Paulo, SP, BrazilLipids Laboratory (LIM 10), Faculty of Medical Sciences, The University of São Paulo, São Paulo, SP, BrazilLaboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Science IV, University of São Paulo, São Paulo, SP, BrazilLaboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Science IV, University of São Paulo, São Paulo, SP, BrazilLipids Laboratory (LIM 10), Faculty of Medical Sciences, The University of São Paulo, São Paulo, SP, BrazilLipids Laboratory (LIM 10), Faculty of Medical Sciences, The University of São Paulo, São Paulo, SP, BrazilLaboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Science IV, University of São Paulo, São Paulo, SP, BrazilEmergency Care Research Unit Laboratory (LIM 51), Faculty of Medical Sciences, The University of São Paulo, São Paulo, SP, BrazilLipids Laboratory (LIM 10), Faculty of Medical Sciences, The University of São Paulo, São Paulo, SP, BrazilSepsis is a systemic inflammatory response to infection eliciting high mortality rate which is a serious health problem. Despite numerous studies seeking for therapeutic alternatives, the mechanisms involved in this disease remain elusive. In this study we evaluated the influence of cholesteryl ester transfer protein (CETP), a glycoprotein that promotes the transfer of lipids between lipoproteins, on the inflammatory response in mice. Human CETP transgenic mice were compared to control mice (wild type, WT) after polymicrobial sepsis induced by cecal ligation and puncture (CLP), aiming at investigating their survival rate and inflammatory profiles. Macrophages from the peritoneal cavity were stimulated with LPS in the presence or absence of recombinant CETP for phenotypic and functional studies. In comparison to WT mice, CETP mice showed higher survival rate, lower IL-6 plasma concentration, and decreased liver toll-like receptor 4 (TLR4) and acyloxyacyl hydrolase (AOAH) protein. Moreover, macrophages from WT mice to which recombinant human CETP was added decreased LPS uptake, TLR4 expression, NF-κB activation and IL-6 secretion. This raises the possibility for new therapeutic tools in sepsis while suggesting that lowering CETP by pharmacological inhibitors should be inconvenient in the context of sepsis and infectious diseases.http://dx.doi.org/10.1155/2016/1784014 |
| spellingShingle | Tatiana Martins Venancio Roberta Marcondes Machado Angela Castoldi Mariane Tami Amano Valeria Sutti Nunes Eder Carlos Rocha Quintao Niels Olsen Saraiva Camara Francisco Garcia Soriano Patrícia Miralda Cazita CETP Lowers TLR4 Expression Which Attenuates the Inflammatory Response Induced by LPS and Polymicrobial Sepsis Mediators of Inflammation |
| title | CETP Lowers TLR4 Expression Which Attenuates the Inflammatory Response Induced by LPS and Polymicrobial Sepsis |
| title_full | CETP Lowers TLR4 Expression Which Attenuates the Inflammatory Response Induced by LPS and Polymicrobial Sepsis |
| title_fullStr | CETP Lowers TLR4 Expression Which Attenuates the Inflammatory Response Induced by LPS and Polymicrobial Sepsis |
| title_full_unstemmed | CETP Lowers TLR4 Expression Which Attenuates the Inflammatory Response Induced by LPS and Polymicrobial Sepsis |
| title_short | CETP Lowers TLR4 Expression Which Attenuates the Inflammatory Response Induced by LPS and Polymicrobial Sepsis |
| title_sort | cetp lowers tlr4 expression which attenuates the inflammatory response induced by lps and polymicrobial sepsis |
| url | http://dx.doi.org/10.1155/2016/1784014 |
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