Involvement of tyrosine-specific protein kinase and protein kinase C in J774A.1 macrophage functions activated by Tinospora cordifolia

BACKGROUND: Macrophages are the first line of defense and constitute important participant in the bi-directional interaction between innate and specific immunity. Macrophages are in a quiescent form and get activated when given a stimulus. In our previous studies we have reported that guduchi or LPS treatment of macrophages enhanced production of nitric oxide (NO) and increased tumoricidal activity against L929 fibroblast cells. OBJECTIVE: In the present study effect of Tinospora cordifolia commonly known as guduchi on macrophage activation and the mechanism of action i.e. involvement of protein kinase C inhibitor and tyrosine-specific protein kinase inhibitor was investigated. MATERIALS AND METHODS: The present study was undertaken to determine whether H-7 (inhibitor of protein kinase C) and/or genistein (inhibitor of tyrosine-specific protein kinase) could inhibit guduchi or LPS-induced macrophage NO and TNF-α production or reduce the cytolysis of L929 fibroblast cells. RESULTS: It was observed that in vitro incubation with H-7 and/or genistein completely inhibited guduchi or LPS-induced NO and TNF-α production by macrophages (J774A.1). CONCLUSION: The inhibitory effects of H-7 and/or genistein, suggest that phosphorylation via these kinases may upregulate the NO synthase activity in macrophages.