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Production and Suppress IL-4 and IL-5 Production in Phytohemagglutinin-Stimulated Human T Cells1
Department of Dermatology, School of Medicine, Teikyo University, Tokyo, Japan
Gangliosides are sialic acid-containing glycolipids. We studied the
in vitro effects of gangliosides on Th1 and Th2 cytokine production in
PHA-stimulated human T cells. Gangliosides GD1b, GT1b, and GQ1b (each
100 nM) enhanced PHA-induced IL-2 secretion of peripheral blood T cells
4-fold and enhanced that of IFN-
3- to 4-fold compared with
controls. These gangliosides decreased PHA-induced IL-4 secretion by
50–53% and that of IL-5 by 53–63% compared with controls,
respectively. The other gangliosides did not alter the secretion of Th1
or Th2 cytokines. RT-PCR showed that GD1b, GT1b, and GQ1b enhanced
PHA-induced IL-2 and IFN- transcription and suppressed that of IL-4
and IL-5. Transient transfection assays of Jurkat T cells showed that
GD1b, GT1b, and GQ1b enhanced PHA-induced IL-2 and IFN- promoter
activities but suppressed those of IL-4 and IL-5. The cAMP analogue
dibutyryl cAMP and the cAMP-elevating agents forskolin and
3-isobutyl-1-methylxanthine each reversed GD1b-, GT1b-, and
GQ1b-induced stimulation of IL-2 and IFN- production and inhibition
of IL-4 and IL-5 production at the levels of proteins, transcription,
and promoter activities. GD1b, GT1b, and GQ1b suppressed PHA-induced
increase in cAMP level in T cells. These gangliosides suppressed
PHA-stimulated adenylate cyclase activity in T cells. These results
suggest that GD1b, GT1b, and GQ1b may enhance Th1 cytokine production
while suppressing Th2 production by inhibiting adenylate cyclase
activity.
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