Docosahexaenoic acid changes lipid composition and interleukin-2 receptor signaling in membrane rafts.
Polyunsaturated fatty acids, including docosahexaenoic acid (DHA, 22:6n-3), modulate immune responses and exert beneficial immunosuppressive effects, but the molecular mechanisms inhibiting T-cell activation are not yet elucidated. Lipid rafts have been shown to play an important role in the compartmentalization and modulation of cell signaling. We investigated the role of DHA in modulating the lipid composition in lipid rafts and membrane subdomain distribution of interleukin-2 (IL-2) receptor signaling molecules. We found that DHA altered lipid components of rafts and modified the IL-2-induced Janus kinase-signal transducer and activator of transcription (STAT) signaling pathway by partially displacing IL-2 receptors from lipid rafts. We fractionated plasma membrane subcellular compartments and discovered that certain amounts of STAT5a and STAT5b existed in detergent-resistant plasma membrane fractions of T-cells. After DHA treatment, STAT5a and STAT5b were not detected in lipid raft fractions and were located in detergent-soluble fractions. These data demonstrate for the first time that DHA alters the lipid composition of membrane microdomains and suppresses IL-2 receptor signaling in T-cells. Thus, our data provide evidence for a functional modification in lipid rafts by DHA treatment and explain PUFA-mediated immunosuppressive effects.
Li
Qiurong
Q
Institute of General Surgery, Jinling Hospital, Nanjing 210002, China. liqiurong@yahoo.com
Wang
Meng
M
Tan
Li
L
Wang
Chang
C
Ma
Jian
J
Li
Ning
N
Li
Yousheng
Y
Xu
Guowang
G
Li
Jieshou
J
D002462:Cell Membrane / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000032:analysis; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005227:Fatty Acids / Q000032:analysis; D006801:Humans; D053613:Janus Kinase 1; D053616:Janus Kinase 3; D019169:Jurkat Cells; D013058:Mass Spectrometry; D008563:Membrane Lipids / Q000032:analysis*; D008894:Milk Proteins / Q000032:analysis; D010743:Phospholipids / Q000032:analysis; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000378:metabolism*; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000737:chemistry; D015534:Trans-Activators / Q000032:analysis; D025521:Tumor Suppressor Proteins; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D005227:Fatty Acids; D008563:Membrane Lipids; D008894:Milk Proteins; D010743:Phospholipids; D015375:Receptors, Interleukin-2; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D004281:Docosahexaenoic Acids; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507933:JAK3 protein, human; D053613:Janus Kinase 1; D053616:Janus Kinase 3