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The Antimicrobial Peptide LL-37 Alters Human Osteoblast Ca Handling and Induces Ca(2+)-Independent Apoptosis.

Säll, Johanna LU ; Carlsson, Martin; Gidlöf, Olof LU ; Holm, Anders LU ; Humlén, Johan; Öhman, Jenny LU ; Svensson, Daniel LU ; Nilsson, Bengt-Olof LU and Jönsson, Daniel LU (2013) In Journal of Innate Immunity 5(3). p.290-300
Abstract
The human antimicrobial peptide cathelicidin LL-37 has, besides its antimicrobial properties, also been shown to regulate apoptosis in a cell type-specific manner. Mechanisms involved in LL-37-regulated apoptotic signaling are not identified. Here, we show that LL-37 reduces the human osteoblast-like MG63 cell number and cell viability in the micromolar concentration range with an IC(50) value of about 5 µM. Treatment with 4 µM LL-37 increased the number of annexin V-positive cells and stimulated activation of caspase 3 showing that LL-37 promotes apoptosis. Treatment with 4 µM LL-37 caused an acute and sustained rise in intracellular Ca(2+) concentration assessed by laser-scanning confocal microscopy of Fluo-4-AM-loaded MG63 cells. LL-37... (More)
The human antimicrobial peptide cathelicidin LL-37 has, besides its antimicrobial properties, also been shown to regulate apoptosis in a cell type-specific manner. Mechanisms involved in LL-37-regulated apoptotic signaling are not identified. Here, we show that LL-37 reduces the human osteoblast-like MG63 cell number and cell viability in the micromolar concentration range with an IC(50) value of about 5 µM. Treatment with 4 µM LL-37 increased the number of annexin V-positive cells and stimulated activation of caspase 3 showing that LL-37 promotes apoptosis. Treatment with 4 µM LL-37 caused an acute and sustained rise in intracellular Ca(2+) concentration assessed by laser-scanning confocal microscopy of Fluo-4-AM-loaded MG63 cells. LL-37 increased Ca(2+) also in the presence of the respective L- and T-type voltage-sensitive Ca(2+) channel blockers nifedipine and NiCl(2). LL-37 had no effect on Ca(2+) in cells incubated with Ca(2+)-free solution. LL-37 (4 and 8 µM) reduced the MG63 cell number both in the presence and absence of Ca(2+) in the medium. In conclusion, LL-37 reduces the osteoblast cell number by promoting apoptosis, and furthermore, LL-37 stimulates Ca(2+) inflow via a mechanism independent of voltage-sensitive Ca(2+) channels. Interestingly, LL-37-induced lowering of the cell number seems to be mediated via a mechanism independent of Ca(2+). (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Innate Immunity
volume
5
issue
3
pages
290 - 300
publisher
Karger
external identifiers
  • wos:000317999300010
  • pmid:23406612
  • scopus:84876791989
ISSN
1662-811X
DOI
10.1159/000346587
language
English
LU publication?
yes
id
0e14c714-74e5-4d26-8f40-510478dbe7b7 (old id 3559837)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23406612?dopt=Abstract
date added to LUP
2013-03-04 10:46:45
date last changed
2019-10-06 03:03:23
@article{0e14c714-74e5-4d26-8f40-510478dbe7b7,
  abstract     = {The human antimicrobial peptide cathelicidin LL-37 has, besides its antimicrobial properties, also been shown to regulate apoptosis in a cell type-specific manner. Mechanisms involved in LL-37-regulated apoptotic signaling are not identified. Here, we show that LL-37 reduces the human osteoblast-like MG63 cell number and cell viability in the micromolar concentration range with an IC(50) value of about 5 µM. Treatment with 4 µM LL-37 increased the number of annexin V-positive cells and stimulated activation of caspase 3 showing that LL-37 promotes apoptosis. Treatment with 4 µM LL-37 caused an acute and sustained rise in intracellular Ca(2+) concentration assessed by laser-scanning confocal microscopy of Fluo-4-AM-loaded MG63 cells. LL-37 increased Ca(2+) also in the presence of the respective L- and T-type voltage-sensitive Ca(2+) channel blockers nifedipine and NiCl(2). LL-37 had no effect on Ca(2+) in cells incubated with Ca(2+)-free solution. LL-37 (4 and 8 µM) reduced the MG63 cell number both in the presence and absence of Ca(2+) in the medium. In conclusion, LL-37 reduces the osteoblast cell number by promoting apoptosis, and furthermore, LL-37 stimulates Ca(2+) inflow via a mechanism independent of voltage-sensitive Ca(2+) channels. Interestingly, LL-37-induced lowering of the cell number seems to be mediated via a mechanism independent of Ca(2+).},
  author       = {Säll, Johanna and Carlsson, Martin and Gidlöf, Olof and Holm, Anders and Humlén, Johan and Öhman, Jenny and Svensson, Daniel and Nilsson, Bengt-Olof and Jönsson, Daniel},
  issn         = {1662-811X},
  language     = {eng},
  number       = {3},
  pages        = {290--300},
  publisher    = {Karger},
  series       = {Journal of Innate Immunity},
  title        = {The Antimicrobial Peptide LL-37 Alters Human Osteoblast Ca Handling and Induces Ca(2+)-Independent Apoptosis.},
  url          = {http://dx.doi.org/10.1159/000346587},
  volume       = {5},
  year         = {2013},
}