The Antimicrobial Peptide LL-37 Alters Human Osteoblast Ca Handling and Induces Ca(2+)-Independent Apoptosis.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3559837
- author
- 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
- organization
- publishing date
- 2013
- 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
- pmid:23406612
- ISSN
- 1662-811X
- DOI
- 10.1159/000346587
- project
- Effects of the antimicrobial peptide LL-37 on host cell viability
- 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
- 2016-04-01 10:03:31
- date last changed
- 2022-04-12 01:31:50
@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 = {{https://lup.lub.lu.se/search/files/1522756/3768315.pdf}}, doi = {{10.1159/000346587}}, volume = {{5}}, year = {{2013}}, }