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, 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.
Leung
Kwok-nam
KN
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, Hong Kong, China. knleung@cuhk.edu.hk
Leung
Pui-yin
PY
Kong
Lai-ping
LP
Leung
Po-ki
PK
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D003208:Concanavalin A / Q000494:pharmacology; D003374:Coumarins / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014468:Umbelliferones / Q000737:chemistry / Q000494:pharmacology*
D003374:Coumarins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014468:Umbelliferones; D003208:Concanavalin A; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C007628:esculetin