Host Defense Peptide LL-37 Selectively Reduces Proinflammatory Macrophage Responses
Abstract
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.
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LL37-induced necrotic PMNs do not induce pro-inflammatory cytokines.
“LL37-induced necrotic PMNs do not induce pro-inflammatory cytokines (146, 147).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [147]
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- Authors
- Brown, K. L., Poon, G. F. T., Birkenhead, D., Pena, O. M., Falsafi, R., Dahlgren, C., Karlsson, A., Bylund, J., Hancock, R. E. W., & Johnson, P.
- Affiliations
- University of British Columbia (CA)
- Department of Rheumatology and Inflammation Research, University of Gothenburg , 40530 Gothenburg ,
- University of Gothenburg (SE)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-05-01
- Volume
- 186
- Issue
- 9
- Pages
- 5497-5505
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1902667058
- Cited by
- 163
- References
- 43
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 8 · 2023: 11 · 2022: 14 · 2021: 9 · 2020: 8 · 2019: 11 · 2018: 9 · 2017: 8 · 2016: 14 · 2015: 17 · 2014: 13 · 2013: 14 · 2012: 9
- FWCI
- 11.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (81314)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- LL-37, cathelicidin, antimicrobial peptides, macrophage polarization, M1 macrophages, M2 macrophages, TNF-α, nitric oxide, reactive oxygen species, arginase, alveolar macrophages, peritoneal macrophages, tumor growth inhibition, LPS, immunomodulation
- MeSH terms
- Animals, Cell Differentiation, Cell Separation, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Inflammation, Macrophages, Mice, Inbred C57BL, Nitric Oxide, Phagocytosis, Tumor Necrosis Factor-alpha, Cytokines, Reverse Transcriptase Polymerase Chain Reaction, Antimicrobial Cationic Peptides, Mice, Cathelicidins
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