title: Glucocorticoids alter the lipid and protein composition of membrane rafts of a murine T cell hybridoma.
abstract: Glucocorticoids (GC) are widely used anti-inflammatory agents known to suppress T cell activation by interfering with the TCR activation cascade. The attenuation of early TCR signaling events by these compounds has been recently attributed to a selective displacement of key signaling proteins from membrane lipid rafts. In this study, we demonstrate that GC displace the acyl-bound adaptor proteins linker for activation of T cells and phosphoprotein associated with glycosphingolipid-enriched microdomains from lipid rafts of murine T cell hybridomas, possibly by inhibiting their palmitoylation status. Analysis of the lipid content of the membrane rafts revealed that GC treatment led to a significant decrease in palmitic acid content. Moreover, we found an overall decrease in the proportion of raft-associated saturated fatty acids. These changes were consistent with a decrease in fluorescence anisotropy of isolated lipid rafts, indicating an increase in their fluidity. These findings identify the mechanisms underlying the complex inhibitory effects of glucocorticoids on early TCR signaling and suggest that some of the inhibitory properties of GC on T cell responses may be related to their ability to affect the membrane lipid composition and the palmitoylation status of important signaling molecules.
authors.affiliation: Laboratoire de Physiologie Animale, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Gosselies, Belgium. vanlaetf@mail.nih.gov
authors.forename: François
authors.initials: F
authors.lastname: Van Laethem
authors.forename: Xiquan
authors.initials: X
authors.lastname: Liang
authors.forename: Fabienne
authors.initials: F
authors.lastname: Andris
authors.forename: Jacques
authors.initials: J
authors.lastname: Urbain
authors.forename: Michel
authors.initials: M
authors.lastname: Vandenbranden
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Ruysschaert
authors.forename: Marilyn D
authors.initials: MD
authors.lastname: Resh
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Stulnig
authors.forename: Oberdan
authors.initials: O
authors.lastname: Leo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005227:Fatty Acids / Q000037:antagonists & inhibitors / Q000378:metabolism; D005454:Fluorescence Polarization; D006801:Humans; D006825:Hybridomas; D036341:Intercellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D008560:Membrane Fluidity / Q000187:drug effects / Q000276:immunology; D008563:Membrane Lipids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021962:Membrane Microdomains / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D019308:Palmitic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D005227:Fatty Acids; D036341:Intercellular Signaling Peptides and Proteins; C110810:LAT protein, human; C491734:Lat protein, mouse; D008563:Membrane Lipids; D008565:Membrane Proteins; C498710:PAG1 protein, human; C408344:Pag protein, mouse; D010750:Phosphoproteins; D019308:Palmitic Acid; D003907:Dexamethasone