5-HT1A-mediated promotion of mitogen-activated T and B cell survival and proliferation is associated with increased translocation of NF-kappaB to the nucleus.

ABSTRACT

Mitogenic activation of T and B lymphocytes induces expression of the 5-HT(1A) receptor through an NF-kappaB-dependent signaling pathway. In the present study, it is shown that serotonin (5-HT), as well as the selective 5-HT(1A) receptor agonist R-DPAT, increase cell survival and S phase transition in mouse splenocytes stimulated by T or B cell mitogens. Further examination of the mechanisms underlying increased cell survival revealed that 5-HT and R-DPAT inhibited apoptotic cell death, assessed both by soluble DNA content, internucleosomal DNA cleavage, and hypodiploid DNA content. Additionally, 5-HT and R-DPAT treatment increased intranuclear levels of the p50 and p65 subunits of NF-kappaB. Potentiation by 5-HT and R-DPAT of mitogen-activated cell survival, S phase transition, and nuclear localization of NF-kappaB, as well as inhibition of apoptosis, were all reversed by the selective 5-HT(1A) receptor antagonist WAY-100635. These results indicate that 5-HT(1A)-mediated promotion of cell survival and proliferation of mitogen-activated T and B lymphocytes is associated with increased translocation of NF-kappaB in the nucleus.