Immunomodulatory effects of esculetin (6,7-dihydroxycoumarin) on murine lymphocytes and peritoneal macrophages

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...

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Veröffentlicht in:Cellular & molecular immunology 2005-06, Vol.2 (3), p.181-188
Hauptverfasser: Leung, Kwok-nam, Leung, Pui-yin, Kong, Lai-ping, Leung, Po-ki
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creator Leung, Kwok-nam
Leung, Pui-yin
Kong, Lai-ping
Leung, Po-ki
description 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.
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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. 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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. 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subjects Animals
Cell Movement - drug effects
Cell Proliferation
Concanavalin A - pharmacology
Coumarins - pharmacology
Endocytosis - drug effects
Gene Expression Regulation - drug effects
Killer Cells, Lymphokine-Activated - drug effects
Killer Cells, Lymphokine-Activated - metabolism
Lipopolysaccharides - pharmacology
Lymphocytes - drug effects
Lymphocytes - immunology
Macrophages, Peritoneal - drug effects
Macrophages, Peritoneal - immunology
Mice
Mice, Inbred BALB C
Nitric Oxide - biosynthesis
Nitric Oxide Synthase Type II - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Spleen - drug effects
Spleen - metabolism
Umbelliferones - chemistry
Umbelliferones - pharmacology
title Immunomodulatory effects of esculetin (6,7-dihydroxycoumarin) on murine lymphocytes and peritoneal macrophages
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