Distribution of heat shock proteins in kidneys of rats after immunosuppressive treatment with cyclosporine A

Cyclosporine A (CsA), a fungal undecapeptide, is the most common immunosuppressive drug used in organ transplantation and auto-immune diseases. However, it has severe side effects mainly on renal structures and functions. Therefore, nephrotoxicity is the major limiting side effect. Heat shock proteins (HSPs) are molecular chaperones, that are induced or expressed at high levels in mammalian cells due to a variety of adverse effects. HSPs have beneficial roles in protein processing and protection against cell injury. In the present study, we examined immunohistochemically levels of expression and localization patterns of various HSPs in rat kidneys after administration of a therapeutic CsA dose during 30 days. After CsA treatment, both constitutive HSP 25 and alpha B-crystallin immunoreactivity became stronger in glomeruli, proximal tubules and collecting ducts. Nuclear translocation of these proteins was detected in renal tubules. HSP 47 was detected in the interstitial space between tubules, vascular smooth muscle and medullary rays. Finally, HSP 72 was induced in the cytoplasm of epithelial cells of proximal and distal tubules, and in the cytoplasm of epithelial cells of Henle limbs and collecting ducts. These data demonstrate that CsA clearly induces increased immunoreactivity of HSPs in defined structures of rat kidneys. These findings suggest that these proteins are functionally involved in the defence against renal cellular damage caused by prolonged drug treatment in rat