concanavalin-a and esculetin

Coumarins belong to a diverse group of naturally occurring non-nutrient phytochemicals known as benzo-alpha-pyrones. In this study, esculetin, a 6,7-dihydroxy derivative of coumarin with pleiotropic biological activities, was found to have no significant cytotoxic effect on normal murine macrophages, but it could increase the in vivo migration of the thioglycollate-elicited macrophages in a dose-dependent manner. Moreover, esculetin significantly increased the endocytic activity, and augmented the nitric oxide production and iNOS gene expression in LPS-treated macrophages. In addition, in vivo administration of esculetin into mice was shown to increase the mitogenesis of splenic lymphocytes towards Con A and LPS stimulations, and induced the LAK activity of splenic lymphocytes. Collectively, our results indicate that esculetin could exert immunomodulatory effects on murine macrophages and lymphocytes, both in vitro and in vivo, and this might be one of the possible mechanisms by which coumarins can exert their chemopreventive and anti-tumor activities in vivo.

Topics: Animals; Cell Movement; Cell Proliferation; Concanavalin A; Coumarins; Endocytosis; Gene Expression Regulation; Killer Cells, Lymphokine-Activated; Lipopolysaccharides; Lymphocytes; Macrophages, Peritoneal; Mice; Mice, Inbred BALB C; Nitric Oxide; Nitric Oxide Synthase Type II; RNA, Messenger; Spleen; Umbelliferones

Lipoxygenase inhibitors; eicosatetraynoic acid (ETYA), esculetin and caffeic acid, inhibited interleukin-2 (IL-2) production by Con A (concanavalin A)-stimulated murine spleen lymphocytes. They effectively inhibited IL-2 production without affecting cell viability when they were added to the cultures within around 6 hr after Con A stimulation. IL-1 production was also inhibited effectively when the inhibitors were added within 4 hr after stimulation. Therefore, immunosuppressive characteristics of these inhibitors can in part be explained by their inhibitory effects on production of lymphokines involved in the early phase of lymphocyte activation.

Topics: 5,8,11,14-Eicosatetraynoic Acid; Animals; Arachidonic Acids; Caffeic Acids; Concanavalin A; Female; Interleukin-1; Interleukin-2; Lipoxygenase; Lipoxygenase Inhibitors; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Umbelliferones