Sanglifehrin A, a novel cyclophilin-binding immunosuppressant, inhibits IL-2-dependent T cell proliferation at the G1 phase of the cell cycle

L. H. Zhang, J. O. Liu

Research output: Contribution to journalArticle

Abstract

Sanglifehrin A (SFA) is a novel immunosuppressive natural product that binds to cyclophilin but is structurally distinct from cyclosporin A (CsA). We have investigated the cellular and molecular mechanisms of the action of SFA in T lymphocytes. We show that SFA inhibits T cell proliferation induced by IL-2 with an IC50 of 200 nM. Distinct from CsA, which also binds to cyclophilin, SFA does not affect calcium-dependent IL-2 production, although SFA enhanced IL-2 gene transcription in the same cells. SFA blocks T cell proliferation induced by IL-2 in G1 with no appreciable effect on IL-2 receptor expression in a manner similar to that of the immunosuppressant rapamycin. Unlike rapamycin, however, SFA has no effect on the phosphorylation or enzymatic activity of p70s6k kinase, distinguishing SFA from rapamycin in their mode of action. SFA inhibits hyperphosphorylation of Rb and the activity of cyclin E-cyclin-dependent kinase 2 on IL-2 signaling. These results suggest that SFA has a novel mode of action in comparison with CsA, FK506, and rapamycin, and that its use as a molecular probe may lead to the discovery of a novel target involved in T cell activation.

Original languageEnglish (US)
Pages (from-to)5611-5618
Number of pages8
JournalJournal of Immunology
Volume166
Issue number9
DOIs
StatePublished - May 1 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Sanglifehrin A, a novel cyclophilin-binding immunosuppressant, inhibits IL-2-dependent T cell proliferation at the G<sub>1</sub> phase of the cell cycle'. Together they form a unique fingerprint.

  • Cite this