PROTEIN-KINASE-C - A POTENTIAL PATHWAY OF MACROPHAGE ACTIVATION WITH CISPLATIN

Cisplatin (CP) has been reported to activate murine macrophages to tum oricidal state, however: its mechanism of action is not known. In the present study it is reported that the production of: (a) interleukin-1 (IL-1); (b) tumor necrosis factor (TNF); (c) nitric oxide (NO); and ( d) macrophage-mediated cytotoxicity by cisplatin-treated bone marrow-d erived macrophages were inhibited by PKC inhibitors H-7 and chelerythr ine chloride. Also, it was observed that treatment of macrophages with CP resulted in the translocation of PKC from the cytosol to the membr ane fraction. These findings suggest the involvement of PKC in the act ivation of bone marrow-derived macrophages with cisplatin. (C) 1998 El sevier Science B.V. All rights reserved.