Dexamethasone induces apoptosis in mouse natural killer cells and cytotoxic T lymphocytes.
Glucocorticoid hormones (GCH) induce apoptotic cell death in immature thymocytes through an active mechanism, characterized by extensive DNA fragmentation into oligonucleosomal subunits. This requires macromolecular synthesis and is inhibited by protein kinase C (PKC) inhibitors, interleukin-4 (IL-4) and heat shock (hs). We performed experiments to analyse the possible effect of GCH on more differentiated lymphocytes, i.e. mouse natural killer (NK) cells and CD8+ alloreactive cytotoxic T lymphocytes (CTL). The results show that dexamethasone (DEX) induces DNA fragmentation and cell death in NK cells and CTL in vitro. In both NK cells and CTL, DEX-induced apoptosis is inhibited by IL-2 and IL-4 but, unlike that induced in thymocytes, is augmented by mRNA and protein synthesis inhibitors, PKC inhibitors and HS.
Migliorati
G
G
Institute of Farmacologia Medica, Perugia University Medical School, Italy.
Nicoletti
I
I
D'Adamio
F
F
Spreca
A
A
Pagliacci
C
C
Riccardi
C
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000276:immunology; D004247:DNA / Q000032:analysis; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000648:ultrastructure; D051379:Mice; D008809:Mice, Inbred C3H; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000648:ultrastructure
D007376:Interleukin-2; D015847:Interleukin-4; D003907:Dexamethasone; D004247:DNA