Acute effects of FK506 and cyclosporine A on cultured human proximal tubular cells

Abstract The effects were studied of FK506 and cyclosporine A on human proximal tubular cells. An in vitro assay was used with cultured renal cells which displayed characteristics of proximal tubular cells. Cell growth was measured by [ 3 H]thymidine uptake. FK506 inhibited cell growth by about 50% at 1 μg/ml but cells were not killed as shown by the dye exclusion test. The growth rate of cells recovered to control levels after removal of FK506 from the cultures. FK506 and cyclosporine A showed an additive effect on tubular cell growth reduction. This effect was similar at equivalent doses of FK506 and cyclosporine A, whereas in cultures of leukocytes, the half maximal response to mitogen was obtained at 0.01 μg/ml FK506 and 0.5 μg/ml cyclosporine A, respectively. Immunocytochemistry demonstrated that FK506 reduced the expression of interferon-γ induced major histocompatibility complex (MHC) class I on the proximal tubular cells, but had no effect on the expression of the MHC class II antigens or the intercellular adhesion molecule (ICAM-1) on the cultured cells.