Activation of Murine Peritoneal Macrophages with Cisplatin and Lipopolysaccharide: Involvement of Protein Kinase C and Tyrosine Kinase.

In the present study we report that protein kinase C (PKC) inhibitors, H-7 and chelerythrine chloride, inhibit the cisplatin- or lipopolysaccharide (LPS)-induced activation of murine peritoneal macrophages to the tumoricidal state. Similarly, the tumoricidal activity was also downregulated by protein tyrosine kinase (PTK) inhibitors, genestein and lavendustin A. The production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) by cisplatin- or LPS-treated macrophages was also inhibited by both PKC and PTK inhibitors. These findings suggest the involvement of PKC and PTK in the activation of murine peritoneal macrophages with cisplatin and LPS.