| Cathelicidin Peptide LL-37 Modulates TREM-1 Expression and Inflammatory Responses to Microbial Compounds. | |
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MedLine Citation:
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PMID: 20811938 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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Gimano D Amatngalim; Anastasia Nijnik; Pieter S Hiemstra; Robert E W Hancock |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Inflammation Volume: 34 ISSN: 1573-2576 ISO Abbreviation: Inflammation Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-09-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7600105 Medline TA: Inflammation Country: United States |
Other Details:
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Languages: eng Pagination: 412-25 Citation Subset: IM |
Affiliation:
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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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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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