Prevention of TCR-mediated apoptosis by the elevation ofcAMP

Autor: Makoto Furutani-Selki, Tomio Tada, Yoshihiro Asano, Sumio Hoshi, Masao Seto
Rok vydání: 1994
Předmět:
Zdroj: International Immunology. 6:1081-1090
ISSN: 1460-2377
0953-8178
DOI: 10.1093/intimm/6.7.1081
Popis: The stimulation through TCR-CD3 complexes by immobilized anti-CD3 antibody induced the production of IL-2 and activation-induced cell death (ACD) in the majority of T cell hybridomas. However, some hybridomas produced IL-2 without showing any signs of ACD by the same stimulation, indicating that TCR-CD3-mediated signaling pathways of IL-2 production and of ACD are different. These pathways were discriminated from each other by protein kinase inhibitors and cAMP-elevating reagents such as forskolin. The pathway of IL-2 production but not of ACD was inhibited by protein kinase inhibitors. On the other hand, various cAMP-elevating reagents prevented the T cell hybridomas from TCR-mediated ACD with minimal inhibition of IL-2 production. The elevated cytoplasmic cAMP did not block dexamethasone-induced apoptosis. This indicates that apoptosis is regulated by multiple pathways. Furthermore, the inhibitory effect of cAMP is specific for the TCR-mediated signaling pathway of ACD. Messenger RNA for bcl-2 was detected after treatment with forskolin.
Databáze: OpenAIRE