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Identification of Synthetic Host Defense Peptide Mimics That Exert Dual Antimicrobial and Anti-Inflammatory Activities

Identification of Synthetic Host Defense Peptide Mimics That Exert Dual Antimicrobial and... Identification of Synthetic Host Defense Peptide Mimics That Exert Dual Antimicrobial and Anti-Inflammatory Activities Abhigyan Som a , b , Nicolás Navasa b , Avital Percher a , b , Richard W. Scott c , Gregory N. Tew a , b and Juan Anguita a , d , e a Departments of Polymer Science and Engineering b Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts, USA c Polymedix Inc., Radnor, Pennsylvania, USA d CIC bioGUNE, Bizkaia, Spain e Ikerbasque Foundation, Bilbao, Spain ABSTRACT A group of synthetic antimicrobial oligomers, inspired by naturally occurring antimicrobial peptides, were analyzed for the ability to modulate innate immune responses to Toll-like receptor (TLR) ligands. These synthetic mimics of antimicrobial peptides (SMAMPs) specifically reduced cytokine production in response to Staphylococcus aureus and the S. aureus component lipoteichoic acid (LTA), a TLR2 agonist. Anti-inflammatory SMAMPs prevented the induction of tumor necrosis factor (TNF), interleukin 6 (IL-6), and IL-10 in response to S. aureus or LTA, but no other TLR2 ligands. We show that these SMAMPs bind specifically to LTA in vitro and prevent its interaction with TLR2. Importantly, the SMAMP greatly reduced the induction of TNF and IL-6 in vivo in mice acutely infected with S. aureus while simultaneously reducing bacterial loads dramatically (4 log 10 ). Thus, these SMAMPs can eliminate the damage induced by pathogen-associated molecular patterns (PAMPs) while simultaneously eliminating infection in vivo . They are the first known SMAMPs to demonstrate anti-inflammatory and antibacterial activities in vivo . http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical and Vaccine Immunology American Society For Microbiology

Identification of Synthetic Host Defense Peptide Mimics That Exert Dual Antimicrobial and Anti-Inflammatory Activities

Identification of Synthetic Host Defense Peptide Mimics That Exert Dual Antimicrobial and Anti-Inflammatory Activities

Clinical and Vaccine Immunology , Volume 19 (11): 1784 – Nov 1, 2012

Abstract

Identification of Synthetic Host Defense Peptide Mimics That Exert Dual Antimicrobial and Anti-Inflammatory Activities Abhigyan Som a , b , Nicolás Navasa b , Avital Percher a , b , Richard W. Scott c , Gregory N. Tew a , b and Juan Anguita a , d , e a Departments of Polymer Science and Engineering b Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts, USA c Polymedix Inc., Radnor, Pennsylvania, USA d CIC bioGUNE, Bizkaia, Spain e Ikerbasque Foundation, Bilbao, Spain ABSTRACT A group of synthetic antimicrobial oligomers, inspired by naturally occurring antimicrobial peptides, were analyzed for the ability to modulate innate immune responses to Toll-like receptor (TLR) ligands. These synthetic mimics of antimicrobial peptides (SMAMPs) specifically reduced cytokine production in response to Staphylococcus aureus and the S. aureus component lipoteichoic acid (LTA), a TLR2 agonist. Anti-inflammatory SMAMPs prevented the induction of tumor necrosis factor (TNF), interleukin 6 (IL-6), and IL-10 in response to S. aureus or LTA, but no other TLR2 ligands. We show that these SMAMPs bind specifically to LTA in vitro and prevent its interaction with TLR2. Importantly, the SMAMP greatly reduced the induction of TNF and IL-6 in vivo in mice acutely infected with S. aureus while simultaneously reducing bacterial loads dramatically (4 log 10 ). Thus, these SMAMPs can eliminate the damage induced by pathogen-associated molecular patterns (PAMPs) while simultaneously eliminating infection in vivo . They are the first known SMAMPs to demonstrate anti-inflammatory and antibacterial activities in vivo .

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References (53)

Publisher
American Society For Microbiology
Copyright
Copyright © 2012 by the American society for Microbiology.
ISSN
1556-6811
eISSN
1556-679X
DOI
10.1128/CVI.00291-12
pmid
22956655
Publisher site
See Article on Publisher Site

Abstract

Identification of Synthetic Host Defense Peptide Mimics That Exert Dual Antimicrobial and Anti-Inflammatory Activities Abhigyan Som a , b , Nicolás Navasa b , Avital Percher a , b , Richard W. Scott c , Gregory N. Tew a , b and Juan Anguita a , d , e a Departments of Polymer Science and Engineering b Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts, USA c Polymedix Inc., Radnor, Pennsylvania, USA d CIC bioGUNE, Bizkaia, Spain e Ikerbasque Foundation, Bilbao, Spain ABSTRACT A group of synthetic antimicrobial oligomers, inspired by naturally occurring antimicrobial peptides, were analyzed for the ability to modulate innate immune responses to Toll-like receptor (TLR) ligands. These synthetic mimics of antimicrobial peptides (SMAMPs) specifically reduced cytokine production in response to Staphylococcus aureus and the S. aureus component lipoteichoic acid (LTA), a TLR2 agonist. Anti-inflammatory SMAMPs prevented the induction of tumor necrosis factor (TNF), interleukin 6 (IL-6), and IL-10 in response to S. aureus or LTA, but no other TLR2 ligands. We show that these SMAMPs bind specifically to LTA in vitro and prevent its interaction with TLR2. Importantly, the SMAMP greatly reduced the induction of TNF and IL-6 in vivo in mice acutely infected with S. aureus while simultaneously reducing bacterial loads dramatically (4 log 10 ). Thus, these SMAMPs can eliminate the damage induced by pathogen-associated molecular patterns (PAMPs) while simultaneously eliminating infection in vivo . They are the first known SMAMPs to demonstrate anti-inflammatory and antibacterial activities in vivo .

Journal

Clinical and Vaccine ImmunologyAmerican Society For Microbiology

Published: Nov 1, 2012

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