In:
Journal of Innate Immunity, S. Karger AG, Vol. 5, No. 3 ( 2013), 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 〈 sub 〉 50 〈 /sub 〉 value of about 5 µ 〈 smlcap 〉 M 〈 /smlcap 〉 . Treatment with 4 µ 〈 smlcap 〉 M 〈 /smlcap 〉 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 µ 〈 smlcap 〉 M 〈 /smlcap 〉 LL-37 caused an acute and sustained rise in intracellular Ca 〈 sup 〉 2+ 〈 /sup 〉 concentration assessed by laser-scanning confocal microscopy of Fluo-4-AM-loaded MG63 cells. LL-37 increased Ca 〈 sup 〉 2+ 〈 /sup 〉 also in the presence of the respective L- and T-type voltage-sensitive Ca 〈 sup 〉 2+ 〈 /sup 〉 channel blockers nifedipine and NiCl 〈 sub 〉 2 〈 /sub 〉 . LL-37 had no effect on Ca 〈 sup 〉 2+ 〈 /sup 〉 in cells incubated with Ca 〈 sup 〉 2+ 〈 /sup 〉 -free solution. LL-37 (4 and 8 µ 〈 smlcap 〉 M 〈 /smlcap 〉 ) reduced the MG63 cell number both in the presence and absence of Ca 〈 sup 〉 2+ 〈 /sup 〉 in the medium. In conclusion, LL-37 reduces the osteoblast cell number by promoting apoptosis, and furthermore, LL-37 stimulates Ca 〈 sup 〉 2+ 〈 /sup 〉 inflow via a mechanism independent of voltage-sensitive Ca 〈 sup 〉 2+ 〈 /sup 〉 channels. Interestingly, LL-37-induced lowering of the cell number seems to be mediated via a mechanism independent of Ca 〈 sup 〉 2+ 〈 /sup 〉 .
Type of Medium:
Online Resource
ISSN:
1662-811X
,
1662-8128
Language:
English
Publisher:
S. Karger AG
Publication Date:
2013
detail.hit.zdb_id:
2455818-7
