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 murine peritoneal macrophages produce oncostatin M (OSM) and what is the underlying mechanism. The culture supernatants of cisplatin-treated macrophages significantly inhibited the proliferation of OSM-sensitive cell line A375. Within 15 min of cisplatin treatment significant OSM was synthesized and secreted by macrophages. Inhibitors of serine/threonine and protein tyrosine phosphatases augmented cisplatin-induced OSM production of macrophages. The protein kinase C and protein tyrosine kinase inhibitors significantly inhibited OSM production of cisplatin-treated macrophages. The OSM production of cisplatin-treated macrophages was also inhibited in the presence of Ca2+ chelators, Ca2+ channel blocker and calmodulin/calmodulin-dependent kinase inhibitors. These data suggest that OSM production of cisplatin-treated macrophages is regulated by opposing actions of phosphatases and kinases. It is also suggested that OSM production of cisplatin-treated macrophages is dependent on Ca2+, calmodulin and calmodulin-dependent kinase.
School of Biotechnology, Banaras Hindu University, Varanasi, India.
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Singh
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Sodhi
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology*; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007700:Kinetics; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002147:Calmodulin; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; C508351:OSM protein, human; C508352:Osm protein, mouse; D010455:Peptides; D053683:Oncostatin M; D011505:Protein-Tyrosine Kinases; D010749:Phosphoprotein Phosphatases; D017027:Protein Tyrosine Phosphatases; D002945:Cisplatin; D002118:Calcium