The Antimicrobial Peptide LL-37 Alters Human Osteoblast Ca Handling and Induces Ca(2+)-Independent Apoptosis.
Författare
Summary, in English
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+).
Publiceringsår
2013
Språk
Engelska
Sidor
290-300
Publikation/Tidskrift/Serie
Journal of Innate Immunity
Volym
5
Issue
3
Fulltext
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Karger
Ämne
- Immunology in the medical area
Status
Published
Projekt
- Effects of the antimicrobial peptide LL-37 on host cell viability
Forskningsgrupp
- Vascular Physiology
ISBN/ISSN/Övrigt
- ISSN: 1662-811X