CISPLATIN-TREATED MACROPHAGES PRODUCE ONCOSTATIN-M - REGULATION BY SERINE THREONINE AND PROTEIN-TYROSINE KINASES/PHOSPHATASES AND CA2+/CALMODULIN/

In the present study it was investigated whether cisplatin-treated mur ine peritoneal macrophages produce oncostatin M (OSM) and what is the underlying mechanism. The culture supernatants of cisplatin-treated ma crophages significantly inhibited the proliferation of OSM-sensitive c ell line A375. Within 15 min of cisplatin treatment significant OSM wa s synthesized and secreted by macrophages. Inhibitors of serine/threon ine and protein tyrosine phosphatases augmented cisplatin-induced OSM production of macrophages. The protein kinase C and protein tyrosine k inase inhibitors significantly inhibited OSM production of cisplatin-t reated macrophages. The OSM production of cisplatin-treated macrophage s was also inhibited in the presence of Ca2+ chelators, Ca2+ channel b locker and calmodulin/calmodulin-dependent kinase inhibitors. These da ta suggest that OSM production of cisplatin-treated macrophages is reg ulated by opposing actions of phosphatases and kinases. It is also sug gested that OSM production of cisplatin-treated macrophages is depende nt on Ca2+, calmodulin and calmodulin-dependent kinase. (C) 1998 Elsev ier Science B.V. All rights reserved.