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 immunosupp ressive drug used in organ transplantation and auto-immune diseases. Howeve r, it has severe side effects mainly on renal structures and functions. The refore, nephrotoxicity is the major limiting side effect. Heat shock protei ns (HSPs) are molecular chaperones, that are induced or expressed at high l evels in mammalian cells due to a variety of adverse effects. HSPs have ben eficial roles in protein processing and protection against cell injury. In the present study, we examined immunohistochemically levels of expression a nd localization patterns of various HSPs in rat kidneys after administratio n of a therapeutic CsA dose during 30 days. After CsA treatment, both const itutive HSP 25 and alpha B-crystallin immunoreactivity became stronger in g lomeruli, proximal tubules and collecting ducts. Nuclear translocation of t hese proteins was detected in renal tubules. HSP 47 was detected in the int erstitial space between tubules, vascular smooth muscle and medullary rays. Finally, HSP 72 was induced in the cytoplasm of epithelial cells of proxim al and distal tubules, and in the cytoplasm of epithelial cells of Henle li mbs and collecting ducts. These data demonstrate that CsA clearly induces i ncreased immuno-reactivity of HSPs in defined structures of rat kidneys. Th ese findings suggest that these proteins are functionally involved in the d efence against renal cellular damage caused by prolonged drug treatment in rat.