GRP78 INDUCTION BY CYCLOSPORINE-A IN HUMAN HELA-CELLS

Immunosuppressive drugs such as cyclosporin A (CsA) and FK506 are know n to have pleiotropic effects on cells. Here we demonstrate that treat ment of HeLa cells with low concentrations of CsA (but not of FK506) i nduces the synthesis of a stress protein, GRP78, located inside the en doplasmic reticulum. High concentrations of CsA lead to a general decr ease in protein synthesis. When cells are stressed (heat-shocked) duri ng the CsA treatment, the synthesis of heat shock proteins is reinforc ed. FK506 has no detectable effects at any concentration. The mechanis m of induction of GRP78 by CsA remains presently unknown. Whatever the mechanism involved, GRP78 overexpression might be responsible for som e of the physiological effects of CsA.