Co-administration of antimicrobial peptides enhances toll-like receptor 4 antagonist activity of a synthetic glycolipid

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• dc.contributor.author Facchini, Fabio A.ca
• dc.contributor.author Coelho, Helenaca
• dc.contributor.author Sestito, Stefania Enzaca
• dc.contributor.author Delgado, Sandraca
• dc.contributor.author Minotti, Albertoca
• dc.contributor.author Andreu Martínez, Davidca
• dc.contributor.author Jiménez-Barbero, Jesús J.ca
• dc.contributor.author Peri, Francescoca
• dc.date.accessioned 2018-04-12T07:25:39Z
• dc.date.available 2018-04-12T07:25:39Z
• dc.date.issued 2018
• dc.description.abstract This study examines the effect of co-administration of antimicrobial peptides and the synthetic glycolipid FP7, which is active in inhibiting inflammatory cytokine production caused by TLR4 activation and signaling. The co-administration of two lipopolysaccharide (LPS)-neutralizing peptides (a cecropin A-melittin hybrid peptide and a human cathelicidin) enhances by an order of magnitude the potency of FP7 in blocking the TLR4 signal. Interestingly, this is not an additional effect of LPS neutralization by peptides, because it also occurs if cells are stimulated by the plant lectin phytohemagglutinin, a non-LPS TLR4 agonist. Our data suggest a dual mechanism of action for the peptides, not exclusively based on LPS binding and neutralization, but also on a direct effect on the LPS-binding proteins of the TLR4 receptor complex. NMR experiments in solution show that peptide addition changes the aggregation state of FP7, promoting the formation of larger micelles. These results suggest a relationship between the aggregation state of lipid A-like ligands and the type and intensity of the TLR4 response.
• dc.description.sponsorship This study was financially supported by the H2020‐MSC‐ETN‐642157 project TOLLerant. The Italian Ministry for Foreign Affairs and International Cooperation (MAECI) is acknowledged. Work at Pompeu Fabra University was supported by MINECO (grants SAF2011‐24899, AGL2014‐52395‐C2‐2‐R to D.A., CTQ2015‐64597‐C2‐1‐P and MINECO‐Severo Ochoa Excellence Acreditation 2017-2021 (SEV‐2016‐0644) to J.J.‐B.) with FEDER funds, and by Generalitat de Catalunya (2014SGR692).
• dc.format.mimetype application/pdf
• dc.identifier.citation Facchini FA, Coelho H, Sestito SE, Delgado S, Minotti A, Andreu D et al. Co-administration of Antimicrobial Peptides Enhances Toll-like Receptor 4 Antagonist Activity of a Synthetic Glycolipid. ChemMedChem. 2018 Feb 6;13(3):280-7. DOI: 10.1002/cmdc.201700694
• dc.identifier.doi http://dx.doi.org/10.1002/cmdc.201700694
• dc.identifier.issn 1860-7179
• dc.identifier.uri http://hdl.handle.net/10230/34344
• dc.language.iso eng
• dc.publisher Wiley-VCH Verlagca
• dc.relation.ispartof ChemMedChem. 2018 Feb 6;13(3):280-7
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/642157
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011‐24899
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/AGL2014‐52395‐C2‐2‐R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/CTQ2015‐64597‐C2‐1‐P
• dc.rights © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword FP7
• dc.subject.keyword Aggregation
• dc.subject.keyword Antimicrobial peptides
• dc.subject.keyword Small-molecule antagonists
• dc.subject.keyword Toll-like receptor 4
• dc.title Co-administration of antimicrobial peptides enhances toll-like receptor 4 antagonist activity of a synthetic glycolipidca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion