Mechanisms of the innate defense regulator peptide-1002 anti-inflammatory activity in a sterile inflammation mouse model

Bing Catherine Wu, Amy Huei Yi Lee, Robert E.W. Hancock

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Innate defense regulator (IDR) peptide-1002 is a synthetic host defense peptide derivative with strong anti-inflammatory properties. Extending previous data, IDR-1002 suppressed in vitro inflammatory responses in RAW 264.7 murine monocyte/macrophage cells challenged with the TLR4 agonist LPS and TLR2 agonists lipoteichoic acid and zymosan. To investigate the anti-inflammatory mechanisms of IDR-1002 in vivo, the PMA-induced mouse ear inflammation model was used. Topical IDR-1002 treatment successfully dampened PMA-induced ear edema, proinflammatory cytokine production, reactive oxygen and nitrogen species release, and neutrophil recruitment in the ears of CD1 mice. Advanced RNA transcriptomic analysis on the mouse ear transcriptome revealed that IDR-1002 reduced sterile inflammation by suppressing the expression of transmembrane G protein-coupled receptors (class A/1 rhodopsin-like), including receptors for chemokines, PGs, histamine, platelet activating factor, and anaphylatoxin. IDR-1002 also dampened the IFN-g response and repressed the IFN regulatory factor 8-regulated network that controls central inflammatory pathways. This study demonstrates that IDR-1002 exhibits strong in vitro and in vivo anti-inflammatory activities, informs the underlying anti-inflammatory mechanisms, and reveals its potential as a novel therapeutic for inflammatory diseases.

Original languageEnglish
Pages (from-to)3592-3603
Number of pages12
JournalJournal of Immunology
Volume199
Issue number10
DOIs
Publication statusPublished - 15 Nov 2017

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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