Apoptosis-induced inhibition of CD1d-mediated antigen presentation: different roles for caspases and signal transduction pathways
AuthorsKhan, Masood A.
Renukaradhya, Gourapura J.
Brutkiewicz, Randy R.
UMass Chan AffiliationsDepartment of Microbiology and Immunology
Graduate School of Biomedical Sciences
KeywordsAnimals; Antigen Presentation; Antigens, CD1; Antigens, CD1d; Apoptosis; Camptothecin; Caspases; Cells, Cultured; Ceramides; Coculture Techniques; Female; Galactosylceramides; Meperidine; Mice; Mice, Inbred C57BL; Protein Kinase C-delta; Signal Transduction; p38 Mitogen-Activated Protein Kinases
Medicine and Health Sciences
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AbstractThe stimulation of programmed cell death can either enhance or inhibit antigen presentation by classic major histocompatibility complex molecules. In the current study, we report that the induction of apoptosis by topoisomerase I inhibition or elevation of intracellular ceramide levels substantially impairs CD1d-mediated antigen presentation. In the former case, such a reduction occurred via the regulation of both the p38 mitogen-activated protein kinases and protein kinase C delta signal transduction pathways as well as the caspase cascade, whereas the latter was p38-(but not caspase)-dependent. Confocal microscopic analysis showed an altered intracellular distribution of CD1d following the inhibition topoisomerase I or by an increase in intracellular ceramide levels, that was prevented by p38 and caspase inhibitors. Thus, the induction of apoptosis in antigen presenting cells severely compromises CD1d-mediated antigen presentation by multiple mechanisms.
SourceImmunology. 2008 Sep;125(1):80-90. Epub 2008 Mar 14. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/32914
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