Role of serotonin in the regulation of interferon-gamma production by human natural killer cells.
Monocytes, recovered directly from peripheral blood by counter-current centrifugal elutriation (CCE), were shown to provide two regulatory signals for induction of interferon-gamma (IFN-gamma) in natural killer (NK) cells in response to interleukin-2 (IL-2): an upregulating signal and an inhibitory signal. The inhibitory signal was time-dependent, irreversible, and operating on a pretranslational level, as indicated by the inability of enriched NK cells to accumulate IFN-gamma mRNA in the presence of elutriated monocytes. Monocyte-induced inhibition of IFN-gamma production was abrogated by the biogenic amine serotonin, acting via the 5-hydroxytryptamine, or serotonin (5-HT1A), subset of serotonin receptors (5-HTR). Thereby, serotonin effectively promoted IFN-gamma production in the presence of monocytes. We conclude that serotonergic 5-HT1A receptors transduce signals that are required for NK cells to produce IFN-gamma in response to IL-2.
Hellstrand
K
K
Department of Clinical Virology, University of Göteborg, Sweden.
Czerkinsky
C
C
Ricksten
A
A
Jansson
B
B
Asea
A
A
Kylefjord
H
H
Hermodsson
S
S
D002450:Cell Communication / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D007694:Killer Cells, Natural / Q000378:metabolism*; D009000:Monocytes / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D012333:RNA, Messenger; D011985:Receptors, Serotonin; D012701:Serotonin; D007371:Interferon-gamma