The Hsp90-specific inhibitor, geldanamycin, blocks CD28-mediated activation of human T lymphocytes

Life Sci. 1998;63(11):949-54. doi: 10.1016/s0024-3205(98)00352-x.

Abstract

The 90 kDa heat shock protein (Hsp90) is a molecular chaperone aiding the folding of nuclear hormone receptors and protein kinases. Hsp90-mediated folding can be disrupted by the Hsp90-specific drug, geldanamycin. Here we provide evidence for the inhibition of the CD28-specific BW 828 antibody-mediated activation of human T lymphocyte proliferation, IL-2 secretion and IL-2 receptor expression by geldanamycin. Our results suggest that the major cytoplasmic chaperone, Hsp90, plays an important role in CD28-mediated T lymphocyte activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Blocking / pharmacology
  • Benzoquinones
  • CD28 Antigens / immunology
  • CD28 Antigens / pharmacology*
  • Enzyme Inhibitors / pharmacology*
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP90 Heat-Shock Proteins / physiology
  • Humans
  • Interleukin-2 / metabolism
  • Lactams, Macrocyclic
  • Lymphocyte Activation / drug effects
  • Quinones / pharmacology*
  • Receptors, Interleukin-2 / biosynthesis
  • Signal Transduction
  • T-Lymphocytes / immunology*

Substances

  • Antibodies, Blocking
  • Benzoquinones
  • CD28 Antigens
  • Enzyme Inhibitors
  • HSP90 Heat-Shock Proteins
  • Interleukin-2
  • Lactams, Macrocyclic
  • Quinones
  • Receptors, Interleukin-2
  • geldanamycin