Apolipoprotein CI enhances the biological response to LPS via the CD14/TLR4 pathway by LPS-binding elements in both its N- and C-terminal helix
| Autor: | Louis M. Havekes, Jimmy F.P. Berbée, Claudia P. Coomans, Marit Westerterp, Johannes A. Romijn, Patrick C.N. Rensen |
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| Přispěvatelé: | Center for Liver, Digestive and Metabolic Diseases (CLDM), Translational Immunology Groningen (TRIGR), TNO Kwaliteit van Leven, General Internal Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Lipopolysaccharides
Models Molecular Secondary Biomedical Research endotoxins Lipopolysaccharide Mouse Lipopolysaccharide Receptors Carboxy terminal sequence Plasma protein binding Signal transduction Inbred C57BL Peptides/chemistry Biochemistry Protein Structure Secondary Mice chemistry.chemical_compound Endocrinology Amino terminal sequence Models Tnfα TNFα Receptor Research Articles Peritoneum macrophage Toll like receptor 4 peptide Peptide lipids (amino acids peptides and proteins) Animal cell Lipopolysaccharide binding protein Protein Binding Protein Structure mice peptide inflammation endotoxins TNF alpha mice low-density lipoproteins inflammatory response angstrom resolution scavenger receptors crystal-structure lipopolysaccharide protein endotoxin sepsis peptide CD14 Molecular Sequence Data Apolipoprotein C1 Plasma clearance QD415-436 Biology Proinflammatory cytokine Cell Line Electrophoretic mobility Animals Lipopolysaccharide Receptors/immunology Lipopolysaccharides/immunology Animal experiment Amino Acid Sequence Cytokine release Inflammation Apolipoprotein C-I Signal Transduction/immunology Tumor Necrosis Factor-alpha Tumor necrosis factor alpha Macrophages Toll-Like Receptor 4/immunology Molecular Macrophages/cytology Cell Biology CD14 antigen Nonhuman Tumor Necrosis Factor-alpha/immunology Molecular biology Endotoxins Toll-Like Receptor 4 Mice Inbred C57BL chemistry inflammation TLR4 biology.protein Apolipoprotein C-I/chemistry Peptides Controlled study Sequence Alignment |
| Zdroj: | Journal of Lipid Research, Vol 51, Iss 7, Pp 1943-1952 (2010) Journal of Lipid Research, 51(7), 1943-1952. AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC Journal of Lipid Research, 51(7), 1943-1952 Journal of lipid research, 51(7), 1943-1952. American Society for Biochemistry and Molecular Biology Inc. Journal of Lipid Research, 7, 51, 1943-1952 |
| ISSN: | 0022-2275 |
| Popis: | Timely sensing of lipopolysaccharide (LPS) is critical for the host to fight invading Gram-negative bacteria. We recently showed that apolipoprotein CI (apoCI) (apoCI(1-57)) avidly binds to LPS, involving an LPS-binding motif (apoCI(48-54)), and thereby enhances the LPS-induced inflammatory response. Our current aim was to further elucidate the structure and function relationship of apoCI with respect to its LPS-modulating characteristics and to unravel the mechanism by which apoCI enhances the biological activity of LPS. We designed and generated N- and C-terminal apoCI-derived peptides containing varying numbers of alternating cationic/hydrophobic motifs. ApoCI(1-38), apoCI(1-30), and apoCI(35-57) were able to bind LPS, whereas apoCI(1-23) and apoCI(46-57) did not bind LPS. In line with their LPS-binding characteristics, apoCI(1-38), apoCI(1-30), and apoCI(35-57) prolonged the serum residence of I-125-LPS by reducing its association with the liver. Accordingly, both apoCI(1-30) and apoCI(35-57) enhanced the LPS-induced TNF alpha response in vitro (RAW 264.7 macrophages) and in vivo (C57Bl/6 mice). Additional in vitro studies showed that the stimulating effect of apoCI on the LPS response resembles that of LPS-binding protein (LBP) and depends on CD14/ Toll-like receptor 4 signaling.(jlr) We conclude that apoCI contains structural elements in both its N-terminal and C-terminal helix to bind LPS and to enhance the proinflammatory response toward LPS via a mechanism similar to LBP.-Berbee, J. F. P., C. P. Coomans, M. Westerterp, J. A. Romijn, L. M. Havekes, and P. C. N. Rensen. Apolipoprotein CI enhances the biological response to LPS via the CD14/TLR4 pathway by LPS-binding elements in both its N- and C-terminal helix. J. Lipid Res. 2010. 51: 1943-1952 |
| Databáze: | OpenAIRE |
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