Host defense peptide LL-37 selectively reduces proinflammatory macrophage responses

The human cathelicidin peptide, LL-37, is a host defense peptide with a wide range of immunomodulatory activities and modest direct antimicrobial properties. LL-37 can exert both pro- and anti-inflammatory effects and can modulate the proinflammatory responses of human peripheral blood monocytes and...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2011-05, Vol.186 (9), p.5497-5505
Main Authors: Brown, Kelly L, Poon, Grace F T, Birkenhead, Darlene, Pena, Olga M, Falsafi, Reza, Dahlgren, Claes, Karlsson, Anna, Bylund, Johan, Hancock, Robert E W, Johnson, Pauline
Format: Article
Language:English
Subjects:
Animals
Antimicrobial Cationic Peptides - immunology
Antimicrobial Cationic Peptides - metabolism
Cell Differentiation - immunology
Cell Separation
Cytokines - biosynthesis
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Humans
Immunologi inom det medicinska området
Immunology in the medical area
Inflammation - immunology
Inflammation - metabolism
Macrophages - cytology
Macrophages - immunology
Macrophages - metabolism
Mice
Mice, Inbred C57BL
Microbiology in the medical area
Mikrobiologi inom det medicinska området
Nitric Oxide - biosynthesis
Nitric Oxide - immunology
Phagocytosis - immunology
Reverse Transcriptase Polymerase Chain Reaction
Tumor Necrosis Factor-alpha - biosynthesis
Tumor Necrosis Factor-alpha - immunology
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Summary:The human cathelicidin peptide, LL-37, is a host defense peptide with a wide range of immunomodulatory activities and modest direct antimicrobial properties. LL-37 can exert both pro- and anti-inflammatory effects and can modulate the proinflammatory responses of human peripheral blood monocytes and epithelial cells. In this study, we evaluated the effect of LL-37 on mouse bone marrow-derived macrophages (BMDM) and tissue macrophages in vitro and in vivo. LL-37 dramatically reduced TNF-α and NO levels produced by LPS and IFN-γ-polarized M1-BMDM and slightly reduced reactive oxygen species production by these cells. LL-37 did not affect the ability of IL-4-polarized M2-BMDM to upregulate arginase activity, although it did inhibit LPS-induced TNF-α secretion in these cells. LL-37 did not compromise the ability of M1-polarized BMDM to phagocytose and kill bacteria and did not affect the uptake of apoptotic neutrophils by M2-polarized BMDM. However, LL-37-treated M1-BMDM were more efficient at suppressing tumor growth in vitro. LL-37 significantly reduced LPS-induced TNF-α secretion in ex vivo alveolar macrophages, whereas its effect on peritoneal macrophages was much less dramatic. Effective inhibition of LPS-induced TNF-α secretion by alveolar macrophages also occurred in vivo when LL-37 was administered by intratracheal injection. This demonstrates a selective ability of LL-37 to decrease M1-BMDM, M2-BMDM, and tissue macrophage production of the proinflammatory cytokine TNF-α in response to LPS while leaving other crucial anti-inflammatory M1 and M2 macrophage functions unaltered.
ISSN:0022-1767
1550-6606
1550-6606
DOI:10.4049/jimmunol.1002508