title: Beta-galactosylceramide increases and sulfatide decreases cytokine and chemokine production in whole blood cells.
abstract: The glycosphingolipid sulfatide and its immediate precursor beta-galactosylceramide (GalCer) are present in the pancreatic beta-cell in equimolar concentrations and may play a role in islet pathology. Previous studies of mononuclear cells have shown that sulfatide tends to decrease and GalCer tends to increase the production of proinflammatory cytokines. In this study we investigated the influence of various isoforms of sulfatide on the production of cyto- and chemokines and tested whether the opposing effects of GalCer and sulfatide could counter one another in competition assays. PHA-, LPS-, or unstimulated whole blood cultures were incubated with 30 microg/ml of native sulfatide (isolated from pig brains), C:16:0 and C:24:0 analogues of sulfatide, or native GalCer preparations. After 24 h, the supernatant levels of proinflammatory cytokines and chemokines were quantitated by ELISA. The general trend was for the sulfatides to lower the production of the cytokines, and for GalCer to increase it. In competition assays, native sulfatide dampened the stimulatory effects of GalCer but did not abolish cytokine release; GalCer, on the other hand, nullified the effect of native sulfatide at a ratio of four sulfatide molecules to one GalCer molecule. C:16:0 sulfatide appeared to have a stronger effect than C:24:0 sulfatide. The C:16:0 analogue decreased IL-1beta, IL-6, TNF-alpha, MIP-1alpha and IL-8 to 3-56% of control values (P < 0.05-0.01), while GalCer increased their production 2- to 10-fold (P < 0.01). In conclusion, sulfatide decreases the in vitro production of proinflammatory cytokines, whereas GalCer has the opposite effect.
authors.affiliation: Bartholin Institute, Kommunehospitalet, Copenhagen, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Roeske-Nielsen
authors.forename: P
authors.initials: P
authors.lastname: Fredman
authors.forename: J E
authors.initials: JE
authors.lastname: Mansson
authors.forename: K
authors.initials: K
authors.lastname: Bendtzen
authors.forename: K
authors.initials: K
authors.lastname: Buschard
mesh_terms: D000328:Adult; D000818:Animals; D001773:Blood Cells / Q000378:metabolism*; D002478:Cells, Cultured; D018925:Chemokines / Q000097:blood / Q000378:metabolism*; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D005260:Female; D005699:Galactosylceramides / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013433:Sulfoglycosphingolipids / Q000378:metabolism*; D013552:Swine
chemical_list: D018925:Chemokines; D016207:Cytokines; D005699:Galactosylceramides; D013433:Sulfoglycosphingolipids