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Cathelicidin Peptide LL-37 Modulates TREM-1 Expression and Inflammatory Responses to Microbial Compounds.
MedLine Citation:
PMID:  20811938     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Inflammatory diseases remain an important cause of morbidity and mortality. Cathelicidins are immunomodulatory and antimicrobial peptides with potent anti-endotoxic properties. Although the effects of the human cathelicidin LL-37 on cellular responses to Toll-like receptor (TLR) ligands have been investigated, its effects on responses to other pro-inflammatory stimuli have not been well studied. Triggering receptor expressed on myeloid cells (TREM-1) acts to amplify inflammatory responses and plays important roles in the pathogenesis of endotoxemia. In this work, the effects of LL-37 on responses to TREM-1 stimulation, alone and in the presence of a range of microbial compounds, were analyzed. It was shown that in peripheral blood mononuclear cells LL-37 strongly suppressed synergistic responses to TREM-1 and TLR4 stimulation, partly through the inhibition of TREM-1 expression on monocytes; similar effects were observed using the TLR2 ligand lipoteichoic acid. In contrast, LL-37 stimulated TREM-1 upregulation by peptidoglycan (PGN, TLR2 ligand that is also recognized via nucleotide-binding oligomerization domain containing 2 after fragmentation and intracellular uptake), as well as the responses to combined TREM-1 and PGN stimulation, possibly via the p38 mitogen-activated protein kinase pathway. LL-37 did not affect TREM-1-induced neutrophil degranulation or the production of reactive oxygen species and interleukin-8 by neutrophils. These findings provide further insight into the roles of LL-37 during inflammation and may have implications for its in vivo immunomodulatory properties and for the design of synthetic cathelicidin derivatives as anti-inflammatory and anti-endotoxic molecules.
Authors:
Gimano D Amatngalim; Anastasia Nijnik; Pieter S Hiemstra; Robert E W Hancock
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Inflammation     Volume:  34     ISSN:  1573-2576     ISO Abbreviation:  Inflammation     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600105     Medline TA:  Inflammation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  412-25     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, Centre for Microbial Diseases and Immunity Research, University of British Columbia, 2259 Lower Mall Research Station, Vancouver, V6T 1Z4, Canada.
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