Human cholesteryl ester transfer protein lacks lipopolysaccharide transfer activity, but worsens inflammation and sepsis outcomes in mice
العنوان: | Human cholesteryl ester transfer protein lacks lipopolysaccharide transfer activity, but worsens inflammation and sepsis outcomes in mice |
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المؤلفون: | Thomas Gautier, Kevin van Dongen, Émilie Charron, Stéphane Mandard, Valérie Deckert, Jean-Paul Pais de Barros, Hélène Choubley, Jérôme Labbé, Naig Le Guern, Jacques Grober, Alois Dusuel, Laurent Lagrost |
المساهمون: | Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Université de Bourgogne (UB), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Mandard, Stéphane |
المصدر: | Journal of Lipid Research Journal of Lipid Research, American Society for Biochemistry and Molecular Biology, 2020, pp.jlr.RA120000704. ⟨10.1194/jlr.RA120000704⟩ Journal of Lipid Research, Vol 62, Iss, Pp 100011-(2021) Journal of Lipid Research, 2020, pp.jlr.RA120000704. ⟨10.1194/jlr.RA120000704⟩ |
بيانات النشر: | HAL CCSD, 2020. |
سنة النشر: | 2020 |
مصطلحات موضوعية: | 0301 basic medicine, IL-1β, interleukin 1 beta, SIRS, systemic inflammatory response syndrome, Lipopolysaccharide (LPS), PLTP, phospholipid transfer protein, Bacteremia, 030204 cardiovascular system & hematology, Pharmacology, TLR-4, toll-Like receptor 4, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, PMNL, polymorphonuclear Leukocyte, Biochemistry, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, CETPTg mice, transgenic mice expressing human CETP, Phospholipid transfer protein, Plasma Lipid Transfer Proteins, biology, CE, cholesteryl ester, PLTP KO mice, PLTP knocked-out mice, LpB, apolipoprotein B-containing lipoproteins, Sterol metabolism, 3. Good health, RLT, reverse lipopolysaccharide transport, IL-6, interleukin 6, Cholesterol, CLP, cecal ligation and puncture, Cholesteryl ester, LPS, lipopolysaccharide, lipids (amino acids, peptides, and proteins), medicine.symptom, CD14, cluster of differentiation 14, Infection, Plant lipid transfer proteins, Lipopolysaccharide binding protein, Research Article, WBC, white blood cell, Lipoproteins, MCP-1, monocyte chemoattractant protein 1, Inflammation, MIP-2, macrophage inflammatory protein 2, QD415-436, Proinflammatory cytokine, 03 medical and health sciences, ALT, alanine aminotransferase, Sepsis, Cholesterylester transfer protein, medicine, CETP, cholesteryl ester transfer protein, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, Bactericidal/permeability-increasing protein, Cholesterol Ester Transfer Proteins, LBP, lipopolysaccharide binding protein, carbohydrates (lipids), Endotoxins, 030104 developmental biology, chemistry, LT/LBP, lipid transfer/lipopolysaccharide binding protein, biology.protein, LCMS2, liquid chromatography coupled with tandem mass spectrometry, BPI, bactericidal/permeability increasing protein, IL-10, interleukin 10 |
الوصف: | International audience; Bacterial lipopolysaccharides (LPSs or endotoxins) can bind most proteins of the lipid transfer/LPS-binding protein (LT/LBP) family in host organisms. The LPS-bound LT/LBP proteins then trigger either an LPS-induced proinflammatory cascade or LPS binding to lipoproteins that are involved in endotoxin inactivation and detoxification. Cholesteryl ester transfer protein (CETP) is an LT/LBP member, but its impact on LPS metabolism and sepsis outcome is unclear. Here, we performed fluorescent LPS transfer assays to assess the ability of CETP to bind and transfer LPS. The effects of intravenous (iv) infusion of purified LPS or polymicrobial infection (cecal ligation and puncture [CLP]) were compared in transgenic mice expressing human CETP and wild-type mice naturally having no CETP activity. CETP displayed no LPS transfer activity in vitro, but it tended to reduce biliary excretion of LPS in vivo. The CETP expression in mice was associated with significantly lower basal plasma lipid levels and with higher mortality rates in both models of endotoxemia and sepsis. Furthermore, CETPTg plasma modified cytokine production of macrophages in vitro. In conclusion, despite having no direct LPS binding and transfer property, human CETP worsens sepsis outcomes in mice by altering the protective effects of plasma lipoproteins against endotoxemia, inflammation, and infection. |
وصف الملف: | application/pdf |
اللغة: | English |
تدمد: | 0022-2275 |
DOI: | 10.1194/jlr.RA120000704⟩ |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::afd34527c453da1363375ba2659935a9 https://www.hal.inserm.fr/inserm-03052637 |
Rights: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....afd34527c453da1363375ba2659935a9 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 00222275 |
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DOI: | 10.1194/jlr.RA120000704⟩ |