Role of acidic sphingomyelinase in thymol-mediated dendritic cell death.
METHODS
Thymol is a component of several plants with antimicrobial activity. Little is known about the effects of thymol on immune cells of the host. This study addressed the effects of thymol on dendritic cells (DCs), regulators of innate and adaptive immunity.


RESULTS
Immunohistochemistry, Western blotting and fluorescence-activated cell sorting analysis were performed in bone marrow-derived DCs either from wild-type mice or from mice lacking acid sphingomyelinase (ASM⁻/⁻) treated and untreated for 24 h with thymol (2-100 μg/mL). Thymol treatment resulted in activation of ASM, stimulation of ceramide formation, downregulation of anti-apoptotic Bcl-2 and Bcl-xL proteins, activation of caspase 3 and caspase 8, DNA fragmentation as well as cell membrane scrambling. The effects were dependent on the presence of ASM and were lacking in ASM⁻/⁻ mice or in wild-type DCs treated with sphingomyelinase inhibitor amitriptyline.


CONCLUSIONS
Thymol triggers suicidal DC death, an effect mediated by and requiring activation of ASM.
Xuan
Nguyen Thi
NT
Department of Physiology, University of Tübingen, Tübingen, Germany.
Shumilina
Ekaterina
E
Schmid
Evi
E
Bhavsar
Shefalee K
SK
Rexhepaj
Rexhep
R
Götz
Friedrich
F
Gulbins
Erich
E
Lang
Florian
F
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D002518:Ceramides / Q000096:biosynthesis; D053938:DNA Fragmentation; D003713:Dendritic Cells / Q000187:drug effects* / Q000201:enzymology; D015536:Down-Regulation; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D013943:Thymol / Q000494:pharmacology*; D051020:bcl-X Protein / Q000378:metabolism
C494812:Bcl2l1 protein, mouse; D002518:Ceramides; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D013943:Thymol; D013108:Sphingomyelin Phosphodiesterase; C505409:Casp3 protein, mouse; C505526:Casp8 protein, mouse; D053148:Caspase 3; D053181:Caspase 8