Interleukins modulate glucocorticoid-induced thymocyte apoptosis.
Glucocorticoid hormones, calcium ionophores and anti-CD3 monoclonal antibodies induce apoptosis in mouse thymocytes. This type of cell death, which is characterized by an extensive DNA fragmentation into oligonucleosomal subunits, occurs in the intrathymic process of negative selection, and is involved in the deletion of autoreactive T-cells during thymic maturation. A number of cytokines are able to modulate apoptosis, and interleukins, including interleukin-1, interleukin-2, and interleukin-4, play a crucial role in thymic maturation and T-cell development. We tested the effects of several cytokines on the glucocorticoid hormone-induced apoptosis of mouse thymocytes in vitro, and demonstrated that interleukin-1 alpha, interleukin-2, and interleukin-4 inhibit the apoptosis induced by dexamethasone, but that interleukin-3 and interleukin-6 exert no noteworthy effect. Dose-response experiments indicated that interleukin-4 is more potent than interleukin-1 alpha and interleukin-2 in inhibiting dexamethasone-induced apoptosis. Furthermore, interleukin-4 fully inhibited the DNA fragmentation induced by the protein kinase-C activator 12-O-tetradecanoylphorbol-13-acetate, but was ineffective against apoptosis induced by the calcium ionophore A23187. These results suggest that interleukins regulate the thymic selection process by acting as modulators of the negative selection process.
Migliorati
G
G
Institute of Pharmacology, School of Medicine, University of Perugia, Italy.
Pagliacci
C
C
Moraca
R
R
Crocicchio
F
F
Nicoletti
I
I
Riccardi
C
C
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication; D003907:Dexamethasone / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology*
D007378:Interleukins; D000001:Calcimycin; D003907:Dexamethasone; D013755:Tetradecanoylphorbol Acetate