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The host defense pe...
The host defense peptide LL-37 is internalized by human periodontal ligament cells and prevents LPS-induced MCP-1 production
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- Aidoukovitch, Alexandra (författare)
- Lund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Vascular Physiology,Lund University Research Groups,Swedish Public Dental Care of Skåne
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- Anders, Emma (författare)
- Lund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Vascular Physiology,Lund University Research Groups
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- Dahl, Sara (författare)
- Lund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Vascular Physiology,Lund University Research Groups
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- Nebel, Daniel (författare)
- Lund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Vascular Physiology,Lund University Research Groups
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- Svensson, Daniel (författare)
- Karolinska Institute,Lund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Vascular Physiology,Lund University Research Groups
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- Nilsson, Bengt Olof (författare)
- Lund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Vascular Physiology,Lund University Research Groups
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(creator_code:org_t)
- 2019-05-16
- 2019
- Engelska 9 s.
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Ingår i: Journal of Periodontal Research. - : Wiley. - 0022-3484 .- 1600-0765. ; 54:6, s. 662-670
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Objective: The human host defense peptide LL-37 both shows antimicrobial effects and modulates host cell properties. Here, we assess the effects of synthesized LL-37 on lipopolysaccharide (LPS)-induced inflammation in human periodontal ligament (PDL) cells and investigates underlying mechanisms. Background: LL-37 has been detected in the periodontal tissues, but its functional importance for PDL cell innate immune responses is not known. Methods: Human PDL cells were obtained from premolars extracted on orthodontic indications. Cellular pro-inflammatory monocyte chemoattractant protein-1 (MCP-1) mRNA expression was determined using quantitative real-time RT-PCR. MCP-1 protein production was assessed by western blot and ELISA. Internalization of LL-37 by PDL cells was visualized by immunocytochemistry. Nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-κB) activity was assessed by western blot of phosphorylated p65, phosphorylated p105, and IκBα proteins. Binding of LL-37 to PDL cell DNA was determined by isolation and purification of DNA and dot blot for LL-37 immunoreactivity. Results: Treatment with LL-37 (1 µmol/L) for 24 hours prevented LPS-induced stimulation of MCP-1 expression analyzed both on transcript and on protein levels. Stimulation with LL-37 (1 µmol/L) for 24 hours had no effect on toll-like receptor (TLR)2 and TLR4 transcript expression, suggesting that LL-37 acts downstream of the TLRs. Preincubation with LL-37 for 60 minutes followed by stimulation with LPS for 24 hours in the absence of LL-37 completely prevented LPS-evoked MCP-1 transcript expression, implying that LL-37 acts intracellularly and not via binding and neutralization of LPS. In PDL cells stimulated with LL-37 for 60 minutes, the peptide was internalized as demonstrated by immunocytochemistry, suggesting an intracellular mechanism of action. LL-37 immunoreactivity was observed both in the cytosol and in the nucleus. Downregulation of LPS-induced MCP-1 by LL-37 was not mediated by reduction in NF-κB activity as shown by unaltered expression of phosphorylated p65, phosphorylated p105, and IκBα NF-κB proteins in the presence of LL-37. Immunoreactivity for LL-37 was observed in PDL cell DNA treated with but not without 0.1 and 1 µmol/L LL-37 for 60 minutes in vitro. Conclusion: LL-37 abolishes LPS-induced MCP-1 production in human PDL cells through an intracellular, NF-κB-independent mechanism which probably involves direct interaction between LL-37 and DNA.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Odontologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Dentistry (hsv//eng)
Nyckelord
- antimicrobial peptide
- inflammation
- innate immunity
- NF-κB
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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