期刊
PEPTIDES
卷 135, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2020.170432
关键词
Antimicrobial peptides (AMP); Apoptosis; Cathelicidin; Cytotoxicity; Innate immunity
资金
- Alfred Osterlund Foundation
- Swedish Dental Society
- Research Funds for Oral Health Related Research by Region Skane
- Sigurd and Elsa Goljes Minne Foundation
- Novo Nordisk
- Karolinska Institutet
- Gyllenstiernska Krapperupsstiftelsen
LL-37 reduces human MG63 cell viability, induces apoptosis, and increases plasma membrane permeabilization. LL-37-induced cell death is caspase-independent.
The host defense peptide LL-37 is active against both gram-positive and gram-negative bacteria, but it has also been shown to reduce human host cell viability. However, the mechanisms behind LL-37-induced human host cell cytotoxicity are not yet fully understood. Here, we assess if LL-37-evoked attenuation of human osteoblastlike MG63 cell viability is associated with apoptosis, and if the underlying mechanism may involve LL-37 induced plasma membrane permeabilization. MG63 cell viability and plasma membrane permeabilization were investigated by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and by measuring lactate dehydrogenase (LDH) release, respectively. Apoptosis was assessed by the terminal deoxynucleotidyl dUTP nick end labeling (TUNEL) assay and Annexin V flow cytometry, and caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage were determined by Western blot. LL-37 (4 and 10 mu M) reduced both cell number and cell viability, and these effects were associated with a pro-apoptotic effect demonstrated by positive TUNEL staining and Annexin V flow cytometry. LL-37-induced apoptosis was not coupled to either caspase-3 or PARP cleavage, suggesting that LL-37 causes caspase-independent apoptosis in MG63 cells. Both LL 37 and the well-known plasma membrane permeabilizer Triton X-100 reduced cell viability and stimulated LDH release. Triton X-100-treated cells showed positive TUNEL staining, and the detergent accumulated cells in late apoptosis/necrosis. Similar to LL-37, Triton X-100 caused no PARP cleavage. We conclude that LL-37 promotes caspase-independent apoptosis, and that this effect seems coupled to plasma membrane permeabilization in human MG63 cells.
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