Atorvastatin affects interleukin-2 signaling by altering the lipid raft enrichment of the interleukin-2 receptor β chain

Jens Goebel, Barbara Logan, Kathy Forrest, Alexandra Mieczkowski, Thomas L. Roszman, Marsha Wills-Karp

Research output: Contribution to journalArticlepeer-review

Abstract

Although the immunomodulatory properties of statins are in part independent of their lipid-lowering effects, cholesterol is a major component of lipid rafts. We therefore studied the effects of atorvastatin (AS) on the raft enrichment of the interleukin-2 receptor (IL-2R) β chain previously described by us and on early IL-2R signaling events in activated human T cells. We found that concomitant AS exposure during a 3-day stimulation with phytohemagglutinin (PHA) attenuates activation-associated events, such as the enhanced surface expression of the raft marker GM-1 and the induced expression of the activation marker CD25 (the IL-2R α chain). In contrast, brief AS treatment after PHA stimulation increased GM-1 surface expression and virtually abolished the selective raft enrichment of the IL-2R β chain. Although this AS-associated increase in GM-1 expression resembled that seen in the presence of the raft-disrupting cholesterol chelator methyl-β-cyclodextrin (MBCD), the two agents had contrasting effects on the tyrosine phosphorylation of the IL-2R β chain by exogenous IL-2: MBCD essentially abolished this event, whereas AS tended to enhance it and shifted its occurrence out of rafts. We conclude that AS affects IL-2R signaling by altering the raft enrichment of the IL-2R β chain and propose that this effect is one mechanism underlying the immunomodulatory properties of statins.

Original languageEnglish (US)
Pages (from-to)322-328
Number of pages7
JournalJournal of Investigative Medicine
Volume53
Issue number6
DOIs
StatePublished - Sep 2005
Externally publishedYes

Keywords

  • Interleukin-2 receptor
  • Rafts
  • Statins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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