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Immunologic Research
Published in: Immunologic Research 4/2017

01-08-2017 | Original Article

Innate defense regulator IDR-1018 activates human mast cells through G protein-, phospholipase C-, MAPK- and NF-ĸB-sensitive pathways

Authors: Kensuke Yanashima, Panjit Chieosilapatham, Eri Yoshimoto, Ko Okumura, Hideoki Ogawa, François Niyonsaba

Published in: Immunologic Research | Issue 4/2017

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Abstract

Host defense (antimicrobial) peptides not only display antimicrobial activities against numerous pathogens but also exert a broader spectrum of immune-modulating functions. Innate defense regulators (IDRs) are a class of host defense peptides synthetically developed from natural or endogenous cationic host defense peptides. Of the IDRs developed to date, IDR-1018 is more efficient not only in killing bacteria but also in regulating the various functions of macrophages and neutrophils and accelerating the wound healing process. Because mast cells intimately participate in wound healing and a number of host defense peptides involved in wound healing are also known to activate mast cells, this study aimed to investigate the effects of IDR-1018 on mast cell activation. Here, we showed that IDR-1018 induced the degranulation of LAD2 human mast cells and caused their production of leukotrienes, prostaglandins and various cytokines and chemokines, including granulocyte-macrophage colony-stimulating factor, interleukin-8, monocyte chemoattractant protein-1 and -3, macrophage-inflammatory protein-1α and -1β, and tumor necrosis factor-α. Furthermore, IDR-1018 increased intracellular calcium mobilization and induced mast cell chemotaxis. The mast cell activation was markedly suppressed by pertussis toxin, U-73122, U0126, SB203580, JNK inhibitor II, and NF-κB activation inhibitor II, suggesting the involvement of G-protein, phospholipase C, ERK, p38, JNK and NF-κB pathways, respectively, in IDR-1018-induced mast cell activation. Notably, we confirmed that IDR-1018 caused the phosphorylation of MAPKs and IκB. Altogether, the current study suggests a novel immunomodulatory role of IDR-1018 through its ability to recruit and activate human mast cells at the sites of inflammation and wounds.

Highlights

  • We report that IDR-1018 stimulates various functions of human mast cells.
  • IDR-1018-induced mast cell activation is mediated through G protein, PLC, MAPK and NF-κB pathways.
  • IDR-1018 will be a useful therapeutic agent for wound healing.
Appendix
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Metadata
Title
Innate defense regulator IDR-1018 activates human mast cells through G protein-, phospholipase C-, MAPK- and NF-ĸB-sensitive pathways
Authors
Kensuke Yanashima
Panjit Chieosilapatham
Eri Yoshimoto
Ko Okumura
Hideoki Ogawa
François Niyonsaba
Publication date
01-08-2017
Publisher
Springer US
Published in
Immunologic Research / Issue 4/2017
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-017-8932-0

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