Nicotine-mediated signals modulate cell death and survival of T lymphocytes.
The capacity of nicotine to affect the behavior of non-neuronal cells through neuronal nicotinic acetylcholine receptors (nAChRs) has been the subject of considerable recent attention. Previously, we showed that exposure to nicotine activates the nuclear factor of activated T cells (NFAT) transcription factor in lymphocytes and endothelial cells, leading to alterations in cellular growth and vascular endothelial growth factor production. Here, we extend these studies to document effects of nicotine on lymphocyte survival. The data show that nicotine induces paradoxical effects that might alternatively enforce survival or trigger apoptosis, suggesting that depending on timing and context, nicotine might act both as a survival factor or as an inducer of apoptosis in normal or transformed lymphocytes, and possibly other non-neuronal cells. In addition, our results show that, while having overlapping functions, low and high affinity nAChRs also transmit signals that promote distinct outcomes in lymphocytes. The sum of our data suggests that selective modulation of nAChRs might be useful to regulate lymphocyte activation and survival in health and disease.
Oloris
Silvia C S
SC
Integrated Department of Immunology, School of Medicine, University of Colorado, Denver, Denver, CO, USA.
Frazer-Abel
Ashley A
AA
Jubala
Cristan M
CM
Fosmire
Susan P
SP
Helm
Karen M
KM
Robinson
Sally R
SR
Korpela
Derek M
DM
Duckett
Megan M
MM
Baksh
Shairaz
S
Modiano
Jaime F
JF
D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D009538:Nicotine