Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
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Query: UNIPROT:P08908 (
5-HT1A
)
5,574
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Role of serotonin in the regulation of interferon-gamma production by human natural killer cells. 845 8
Serotonin (5-HT) is a neurotransmitter and an immune modulator. In vitro, antidepressants with a serotonergic mode of action have, at concentrations within the therapeutical range, negative immunoregulatory effects, i.e., they increase the production rate of interleukin-10 (IL-10), a negative immunoregulatory cytokine. We have hypothesized that part of these effects may be explained by the serotonergic activities of antidepressants on immunocytes. This study was carried out to examine the effects of 5-HT, p-chlorophenylalanine (PCPA), a 5-HT depleting agent, flesinoxan (a
5-HT1A
agonist), m-chlorophenylpiperazine (mCPP; a 5-HT2A/2C agonist), and ritanserin (a 5-HT2A/2C antagonist) on the production rate of
interferon-gamma
(IFNgamma), a proinflammatory cytokine, and IL-10 by whole blood stimulated with polyclonal activators. The IFNgamma/IL-10 production ratio was computed, since this ratio reflects the pro- versus anti-inflammatory capacity of cultured whole blood. We found that: 1) 5-HT, 150 ng/mL, 1.5 microg/mL, and 15 microg/mL significantly decreased the IFNgamma/IL-10 ratio; 2) PCPA (5 microM) significantly suppressed the production of IFNgamma and IL-10; 3) flesinoxan (15 ng/mL; 1.5 microg/mL) had no significant effects on the production of the above cytokines; and 4) mCPP (2.7 microg/mL) and ritanserin (5.0 microg/mL) suppressed the IFNgamma/IL-10 ratio. It is concluded that intracellular 5-HT may be necessary for an optimal synthesis of IFNgamma and IL-10, and that extracellular 5-HT concentrations at or above serum values may suppress the production of the proinflammatory cytokine IFNgamma. The negative immunoregulatory effects of antidepressive drugs are probably not related to their serotonergic activities.
...
PMID:Effects of serotonin and serotonergic agonists and antagonists on the production of interferon-gamma and interleukin-10. 1086 89