title: 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.
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.
authors: Department of Dermatology, School of Medicine, Teikyo University, Tokyo, Japan. nmk@med.teikyo-u.ac.jp
authors: N
authors: N
authors: Kanda
authors: S
authors: S
authors: Watanabe
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000328:Adult; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D005260:Female; D005732:Gangliosides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D015848:Interleukin-5 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010835:Phytohemagglutinins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D000276:Adjuvants, Immunologic; D005732:Gangliosides; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015848:Interleukin-5; D010835:Phytohemagglutinins; D012333:RNA, Messenger; C033851:ganglioside, GD1b; D015847:Interleukin-4; C016481:trisialoganglioside GT1; C039129:GQ1b ganglioside; D007371:Interferon-gamma; D000242:Cyclic AMP; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases