Sesamin Inhibits Bacterial Formylpeptide-Induced Inflammatory Responses in a Murine Air-Pouch Model and in THP-1 Human Monocytes

The reaction of human leukocytes to chemoattractants is an important component of the host immune response and also plays a crucial role in the development of inflammation. Sesamin has been shown to inhibit lipid peroxidation and regulate cytokine production. In this study, we examined the effect of sesamin on inflammatory responses elicited by the bacterial chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLF) in vitro and in vivo and explored the mechanisms involved. fMLF is recognized by a human G protein-coupled receptor formyl peptide receptor (FPR) on phagocytic leukocytes. Sesamin at concentrations between 12.5 and 50 mu mol/L inhibited fMLF-induced chemotaxis of human monocyte cell line THP-1 differentiated with dibutyryl cyclic AMP (P < 0.01). Similarly, sesamin inhibited FPR-transfected rat basophilic leukemia cell [epitope-tagged human FPR (ETFR) cell] migration toward fMLF (P < 0.01). In fMLF-induced inflammation in a murine air-pouch model, intraperitoneal administration of sesamin (12 mg.kg(-1)-d(-1) for 2 d) suppressed leukocyte infiltration in to the air pouch induced by fMLF [(62.89 +/- 7.93) x 10(4) VS. (19.67 +/- 4.43) x 10(4) cells/air pouch; n = 9; P < 0.001]. Ca2+ mobilization and mitogen-activated protein kinase extracellular signal-regulated kinase (ERK1/2) activation are involved in fMLF-induced leukocyte migration. Pretreatment of ETFR cells with sesamin inhibited fMLF-induced ERK1/2 phosphorylation in a dose-dependent manner but did not affect fMLF-induced Ca2+, flux, Electrophoretic mobility shift assay showed that pretreatment of THP-1 cells with sesamin dose dependently inhibited fMLF-induced nuclear factor-kappa B (NF-kappa B) activation. These results suggest that sesamin inhibits leukocyte activation by fMLF through ERK1/2- and NF-kappa B-related signaling pathways and thus is a potential compound for the management of inflammatory diseases. J. Nutr. 140: 377-381, 2010.