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  • Title: Immunosuppressive effects of the heat shock protein 90-binding antibiotic geldanamycin.
    Author: Sugita T, Tanaka S, Murakami T, Miyoshi H, Ohnuki T.
    Journal: Biochem Mol Biol Int; 1999 Apr; 47(4):587-95. PubMed ID: 10319410.
    Abstract:
    Ansamycin antibiotic, geldanamycin has a unique pharmacological effect to bind to heat shock protein 90 (hsp90) and deplete hsp90 substrates. We investigated the immunopharmacological effects of geldanamycin. Geldanamycin depleted cellular Raf-1 of rat splenic cells without affecting the steady state levels of hsp90 and downstream mitogen activated protein (MAP) kinases, ERK1 and ERK2. In parallel, it inhibited mitogen-induced nuclear factor-kappa B (NF-kappa B) activation in these cells. Geldanamycin also had a potent suppressive effect on recall antigen-induced T cell proliferation, with an IC50 value of 1 nM. In vivo, geldanamycin suppressed the progression of adjuvant-induced arthritis dose-dependently. These results suggest that geldanamycin exerts an immunosuppressive effect partly through destabilizing Raf-1, and raise a new strategy for the prevention of inflammatory diseases.
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