The role of the Src family kinase Lyn in the immunomodulatory activities of cathelicidin peptide LL-37 on monocytic cells

Anastasia Nijnik, Jelena Pistolic, Patricia Cho, Niall C.J. Filewod, Reza Falsafi, Alexander Ramin, Kenneth W. Harder, Robert E.W. Hancock

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Cathelicidin LL-37 is a multifunctional, immunomodulatory and antimicrobial host-defense peptide of the human immune system. Here, we identified the role of SFKs in mediating the chemokine induction activity of LL-37 in monocytic cells. LL-37 induced SFK phosphorylation; and chemical inhibitors of SFKs suppressed chemokine production in response to LL-37 stimulation. SFKs were required for the downstream activation of AKT, but Ca2+-flux and MAPK induction were SFK-inde-pendent. Through systematic siRNA knockdown of SFK members, a requirement for Lyn in mediating LL-37 activity was identified. The involvement of Lyn in cathelicidin activities was further confirmed using Lyn-knockout mouse BMDMs. The role of SFKs and Lyn was also demonstrated in the activities of the synthetic cationic IDR peptides, developed as novel, immunomodulatory therapeutics. These findings elucidate the common molecular mechanisms mediating the chemokine induction activity of natural and synthetic cationic peptides in monocytic cells and identify SFKs as a potential target for modulating peptide responses.

Original languageEnglish
Pages (from-to)599-607
Number of pages9
JournalJournal of Leukocyte Biology
Volume91
Issue number4
DOIs
Publication statusPublished - 1 Apr 2012

Keywords

  • Chemokine
  • Monocyte
  • Signaling pathways

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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