Skip to main content

Effect of docosahexaenoic acid on interleukin-2 receptor signaling pathway in lipid rafts

Science in China Series C volume 49, pages 63–72 (2006)Cite this article

An Erratum to this article was published on 01 February 2007

Abstract

Recent studies have shown that polyunsaturated fatty acids (PUFA) regulated the functions of membrane receptors in T cells and suppressed T cell-mediated immune responses. But the molecular mechanisms of immune regulation are not yet elucidated. Lipid rafts are plasma membrane microdomains, in which many receptors localized. The purpose of this study was to investigate the effect of DHA on IL-2R signaling pathway in lipid rafts. We isolated lipid rafts by discontinuous sucrose density gradient ultracentrifugation, and found that DHA could change the composition of lipid rafts and alter the distribution of key molecules of IL-2R signaling pathway, which transferred from lipid rafts to detergent-soluble membrane fractions. These results revealed that DHA treatment increased the proportion of polyunsaturated fatty acids especially n−3 polyunsaturated fatty acids in lipid rafts and changed the lipid environment of membrane microdomains in T cells. Compared with controls, DHA changed the localization of IL-2R, STAT5a and STAT5b in lipid rafts and suppressed the expression of JAK1, JAK3 and tyrosine phosphotyrosine in soluble membrane fractions. Summarily, this study concluded the effects of DHA on IL-2R signaling pathway in lipid rafts and explained the regulation of PUFAs in T cell-mediated immune responses.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

References

  1. Zurier, R. B., Fatty acids, inflammation and immune response, Prostaglandins Leuk. Essent. Fatty Acids, 1993, 48: 57–62.

    CAS  Google Scholar 

  2. Brouard, C., M Pascaud, M., Effects of moderate dietary supplementations with n−3 fatty acids on macrophage and lymphocyte phospholipids and macrophage eicosanoid synthesis in the rat, Biochim. Biophys. Acta, 1990, 1047: 19–28.

    CAS  PubMed  Google Scholar 

  3. Rossetti, R. G., Seiler, C. M., DeLuca, P. et al., Oral administration of unsaturated fatty acids: Effects on human peripheral blood T lymphocyte proliferation, J. Leuk. Biol., 1997, 62: 438–443.

    CAS  Google Scholar 

  4. Dillon, S. R., Mancini, M., Rosen, A. et al., Annexin V binds to viable B cells and colocalizes with a marker of lipid rafts upon B cell receptor activation, J. Immunol., 2000, 164: 1322–1332.

    CAS  PubMed  Google Scholar 

  5. Stulnig, T. M., Huber, J., Leitinger, N. et al., Polyunsaturated eicosapentaenoic acid displaces proteins from membrane rafts by altering raft lipid composition, J. Biol. Chem., 2001, 276: 37335–37340.

    Article  CAS  PubMed  Google Scholar 

  6. Stefanova, I., Hořejší, V., Ansotegui, I. J. et al., GPI-anchored cell-surface molecules complexed to protein tyrosine kinases, Science, 1991, 254: 1016–1019.

    CAS  PubMed  Google Scholar 

  7. Shenoy-Scaria, A. M., Kwong, J., Fujita, T. et al., Signal transduction through decay-accelerating factor. Interaction of glycosyl-phosphatidylinositol anchor and protein tyrosine kinases p56lck and p59fyn 1, J. Immunol., 1992, 149: 3535–3541.

    CAS  PubMed  Google Scholar 

  8. Moffett, S., Brown, D. A., Linder, M. E., Lipid-dependent targeting of G proteins into rafts, J. Biol. Chem., 2000, 275: 2191–2198.

    Article  CAS  PubMed  Google Scholar 

  9. Gratton, J. P., Fontana, J., O'Connor, D. S. et al., Reconstitution of an endothelial nitric-oxide synthase (eNOS), hsp90, and caveolin-1 complex in vitro. Evidence that hsp90 facilitates calmodulin stimulated displacement of eNOS from caveolin-1, J. Biol. Chem., 2000, 275: 22268–22272.

    Article  CAS  PubMed  Google Scholar 

  10. Stulnig, T. M., Berger, M., Sigmund, T. et al., Polyunsaturated fatty acids inhibit T cell signal transduction by modification of detergent-insoluble membrane domains, J. Cell. Biol., 1998, 43: 637–644.

    Google Scholar 

  11. Holowka, D., Sheets, E. D., Baird, B., Interactions between FcωRI and lipid raft components are regulated by the actin cytoskeleton, J. Cell Sci., 2000, 113: 1009–1019.

    CAS  PubMed  Google Scholar 

  12. Miyazaki, T., Kawahara, A., Fujii, H., Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits, Science, 1994, 266: 1045–1047.

    CAS  PubMed  Google Scholar 

  13. Lin, J. X., Leonard, W. J., The role of STAT5a and STAT5b in signaling by IL-2 family cytokines, Oncogene, 2000, 19: 2566–2576.

    CAS  PubMed  Google Scholar 

  14. Webb, Y., Hermida-Matsumoto, L., Resh, M. D., Inhibition of protein palmitoylation, raft localization, and T cell signaling by 2-bromopalmitate and polyunsaturated fatty acids, J. Biol. Chem., 2000, 275: 261–270.

    CAS  PubMed  Google Scholar 

  15. Ilangumaran, S., Arni, S., van Echten-Deckert, G. et al., Micro-domain-dependent regulation of Lck and Fyn protein-tyrosine kinases in T lymphocyte plasma membranes, Mol. Biol. Cell, 1999, 10: 891–905.

    CAS  PubMed  Google Scholar 

  16. Simons, K., Ikonen, E., Functional rafts in cell membranes, Nature, 1997, 387: 569–572.

    Article  CAS  PubMed  Google Scholar 

  17. Jump, D. B., The Biochemistry of n−3 polyunsaturated fatty acids, J. Biol. Chem., 2002, 277: 8755–8758.

    Article  CAS  PubMed  Google Scholar 

  18. Horejsi, V., Drbal, K., Cebecauer, M., GPI-microdomains: A role in signaling via immunoreceptors, Immunol. Today, 1999, 20: 356–361.

    CAS  PubMed  Google Scholar 

  19. Jolly, C. A., Jiang, Y. H., Chapkin, R. S. et al., Dietary (n−3) polyunsaturated fatty acids suppress murine lymphoproliferation, interleukin-2 secretion, and the formation of diacylglycerol and ceramide, J. Nutr., 1997, 127: 37–43.

    CAS  PubMed  Google Scholar 

  20. Matkó, J., Bodnár, A., Vereb, G., GPI-microdomains (membrane rafts) and signaling of the multi-chain interleukin-2 receptor in human lymphoma/leukemia T cell lines, Eur. J. Biochem., 2002, 269: 1199–1208.

    PubMed  Google Scholar 

  21. Marmor, M. D., Julius, M., Role for lipid rafts in regulating interleukin-2 receptor signaling, Blood, 2001, 98: 1489–1497.

    Article  CAS  PubMed  Google Scholar 

  22. Ju, H., Venema, V. J., Liang, H. et al., Bradykinin activates the Janus-activated kinase/signal transducers and activators of transcription (JAK/STAT) pathway in vascular endothelial cells: Localization of JAK/STAT signaling proteins in plasmalemmal caveolae, Biochem. J., 2000, 351: 257–264.

    Article  CAS  PubMed  Google Scholar 

  23. Goebel, J., Forrest, K., Morford, L. et al., Differential localization of IL-2-and-15 receptor chains in membrane rafts of human T cells, J. Leuk. Biol., 2002, 72: 199–206.

    CAS  Google Scholar 

  24. Vámosi, G., Bodnár, A., Vereb, G. et al., Dietary docosahexaenoic acid suppresses T cell protein kinase c{theta} lipid raft recruitment and IL-2 production, J. Immunol., 2004, 173: 6151–6160.

    Google Scholar 

  25. Heinrich, P. C., Behrmann, I., Muller-Newen, G. et al., Interleukin-6-type cytokine signaling through the gp130/Jak/STAT pathway, Biochem. J., 1998, 334: 297–314.

    CAS  PubMed  Google Scholar 

  26. Darnell, J. E., STATs and gene regulation, Science, 1997, 277: 1630–1635.

    CAS  PubMed  Google Scholar 

  27. Leonard, W. J., O'Shea, J. J., Jaks and STATs: Biological implications, Annu. Rev. Immunol., 1998, 16: 293–314.

    Article  CAS  PubMed  Google Scholar 

  28. Darnell, J. E., Kerr, I. M., Stark, G. R., Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins, Science, 1994, 264: 1415–1421.

    CAS  PubMed  Google Scholar 

  29. Sehgal, P. B., Guo, G. G., Shah, M. et al., Cytokine signaling. STATs in plasma membrane rafts, J. Biol. Chem., 2002, 277: 12067–12074.

    Article  CAS  PubMed  Google Scholar 

  30. Sehgal, P. B., Plasma membrane rafts and chaperones in cytokine/STAT signaling, Acta Biochimica Polonica, 2003, 50: 583–594

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of General Surgery, General Hospital of Nanjing Command, Nanjing, 210002, China

    Li Qiurong, Ma Jian, Tan Li, Li Ning, Li Yousheng & Li Jieshou

  2. National Chromatographic R. & A. Center, Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116011, China

    Wang Chang & Xu Guowang

Authors
  1. Li Qiurong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ma Jian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wang Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li Ning
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Li Yousheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xu Guowang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Li Jieshou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Li Qiurong.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s11427-007-9001-z.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Li, Q., Ma, J., Tan, L. et al. Effect of docosahexaenoic acid on interleukin-2 receptor signaling pathway in lipid rafts. SCI CHINA SER C 49, 63–72 (2006). https://doi.org/10.1007/s11427-005-0014-1

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11427-005-0014-1

Keywords

  • polyunsaurated fatty acids
  • docosahexaenoic acid
  • IL-2 receptor signaling pathway
  • lipid raft