Document Detail

Gangliosides GD1b, GT1b, and GQ1b enhance IL-2 and IFN-gamma production and suppress IL-4 and IL-5 production in phytohemagglutinin-stimulated human T cells.
MedLine Citation:
PMID:  11123278     Owner:  NLM     Status:  MEDLINE    
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.
N Kanda; S Watanabe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  166     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-01-03     Completed Date:  2001-02-08     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  72-80     Citation Subset:  AIM; IM    
Department of Dermatology, School of Medicine, Teikyo University, Tokyo, Japan.
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MeSH Terms
Adenylate Cyclase / antagonists & inhibitors,  metabolism
Adjuvants, Immunologic / antagonists & inhibitors,  pharmacology
Cyclic AMP / metabolism,  physiology
Cyclic AMP-Dependent Protein Kinase Type II
Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors,  metabolism
Enzyme Activation / drug effects,  immunology
Gangliosides / antagonists & inhibitors,  pharmacology*
Immunosuppressive Agents / antagonists & inhibitors,  pharmacology
Interferon-gamma / biosynthesis*
Interleukin-2 / biosynthesis*
Interleukin-4 / antagonists & inhibitors*,  biosynthesis,  secretion
Interleukin-5 / antagonists & inhibitors*,  biosynthesis,  secretion
Jurkat Cells
Lymphocyte Activation* / drug effects
Middle Aged
Phosphoric Diester Hydrolases / metabolism
Phytohemagglutinins / antagonists & inhibitors,  pharmacology*
Promoter Regions, Genetic / drug effects,  genetics,  immunology
RNA, Messenger / antagonists & inhibitors,  biosynthesis
T-Lymphocytes / drug effects,  enzymology,  immunology,  metabolism*
Th1 Cells / drug effects,  metabolism,  secretion
Th2 Cells / drug effects,  metabolism,  secretion
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Gangliosides; 0/Immunosuppressive Agents; 0/Interleukin-2; 0/Interleukin-5; 0/Phytohemagglutinins; 0/RNA, Messenger; 19553-76-5/ganglioside, GD1b; 207137-56-2/Interleukin-4; 59247-13-1/trisialoganglioside GT1; 60-92-4/Cyclic AMP; 68652-37-9/GQ1b ganglioside; 82115-62-6/Interferon-gamma; EC AMP-Dependent Protein Kinase Type II; EC AMP-Dependent Protein Kinases; EC 3.1.4.-/Phosphoric Diester Hydrolases; EC Cyclase

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