Abstract
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 approximately 4-fold and enhanced that of IFN-gamma 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-gamma 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-gamma 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-gamma 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenylyl Cyclase Inhibitors
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Adenylyl Cyclases / metabolism
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Adjuvants, Immunologic / antagonists & inhibitors
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Adjuvants, Immunologic / pharmacology
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Adult
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Cyclic AMP / metabolism
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Cyclic AMP / physiology
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Cyclic AMP-Dependent Protein Kinase Type II
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Enzyme Activation / drug effects
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Enzyme Activation / immunology
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Female
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Gangliosides / antagonists & inhibitors
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Gangliosides / pharmacology*
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Humans
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Immunosuppressive Agents / antagonists & inhibitors
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Immunosuppressive Agents / pharmacology
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Interferon-gamma / biosynthesis*
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Interleukin-2 / biosynthesis*
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Interleukin-4 / antagonists & inhibitors*
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Interleukin-4 / biosynthesis
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Interleukin-4 / metabolism
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Interleukin-5 / antagonists & inhibitors*
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Interleukin-5 / biosynthesis
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Interleukin-5 / metabolism
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Jurkat Cells
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Lymphocyte Activation* / drug effects
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Male
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Middle Aged
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Phosphoric Diester Hydrolases / metabolism
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Phytohemagglutinins / antagonists & inhibitors
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Phytohemagglutinins / pharmacology*
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Promoter Regions, Genetic / drug effects
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Promoter Regions, Genetic / genetics
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Promoter Regions, Genetic / immunology
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RNA, Messenger / antagonists & inhibitors
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RNA, Messenger / biosynthesis
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T-Lymphocytes / drug effects
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T-Lymphocytes / enzymology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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Th1 Cells / drug effects
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Th1 Cells / metabolism
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Th2 Cells / drug effects
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Th2 Cells / metabolism
Substances
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Adenylyl Cyclase Inhibitors
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Adjuvants, Immunologic
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Gangliosides
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Immunosuppressive Agents
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Interleukin-2
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Interleukin-5
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Phytohemagglutinins
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RNA, Messenger
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ganglioside, GD1b
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Interleukin-4
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trisialoganglioside GT1
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GQ1b ganglioside
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Interferon-gamma
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinase Type II
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Cyclic AMP-Dependent Protein Kinases
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Phosphoric Diester Hydrolases
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Adenylyl Cyclases