MECHANISM OF NF-KAPPA-B TRANSLOCATION IN MACROPHAGES TREATED IN-VITROWITH CISPLATIN

In murine peritoneal macrophages cisplatin (cis-dichlorodiammine plati num (II)), a potent chemoimmunotherapeutic drug modulates the expressi on of several cytokines which contain nuclear factor kappa B (NF-kappa B) binding site suggesting the involvement of NF-kappa B in the activ ation process of macrophages by cisplatin. Therefore, we analyzed the effect of cisplatin treatment on NF-kappa B expression and activation in macrophages. The underlying mechanism of NF-kappa B translocation w as also investigated. Cisplatin treatment increased cellular NF-kappa B content in macrophages treated for 60 min. NF-kappa B translocation was biphasic. Cisplatin-induced translocation of NF-kappa B took place within 5 min and reached its optimum by 15 min. A second phase of nuc lear transfer of NF-kappa B was observed at 3 h of cisplatin treatment which was dependent on H2O2 production in cisplatin-treated macrophag es. It was observed that cisplatin-induced NF-kappa B translocation in volves serine/threonine phosphatases 1/2A, protein tyrosine phosphatas es and genestein sensitive protein tyrosine kinase activities. H-7 sen sitive protein kinase C do not fall in the signaling pathway of cispla tin leading to the translocation of NF-kappa B. Both cytosolic and mem brane-associated factors were required for the induction of NF-kappa B translocation by cisplatin in macrophages. (C) 1998 Elsevier Science B.V. All rights reserved.