title: Sesamin inhibits bacterial formylpeptide-induced inflammatory responses in a murine air-pouch model and in THP-1 human monocytes.
abstract: 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 micromol/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 mgkg(-1)d(-1) for 2 d) suppressed leukocyte infiltration into 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]. Ca(2+) 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 Ca(2+) flux. Electrophoretic mobility shift assay showed that pretreatment of THP-1 cells with sesamin dose dependently inhibited fMLF-induced nuclear factor-kappaB (NF-kappaB) activation. These results suggest that sesamin inhibits leukocyte activation by fMLF through ERK1/2- and NF-kappaB-related signaling pathways and thus is a potential compound for the management of inflammatory diseases.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Shanghai, 200031, China.
authors.forename: Youhong
authors.initials: Y
authors.lastname: Cui
authors.forename: Xinwei
authors.initials: X
authors.lastname: Hou
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Lianying
authors.initials: L
authors.lastname: Xie
authors.forename: Lang
authors.initials: L
authors.lastname: Yang
authors.forename: Yingying
authors.initials: Y
authors.lastname: Le
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000378:metabolism; D001491:Basophils / Q000187:drug effects; D003994:Bucladesine; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004149:Dioxoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D007938:Leukemia / Q000188:drug therapy; D017254:Leukemic Infiltration / Q000188:drug therapy*; D017705:Lignans / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D023421:Models, Animal; D009000:Monocytes / Q000187:drug effects*; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D044042:Receptors, Formyl Peptide / Q000378:metabolism; D031685:Sesamum / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D004149:Dioxoles; D017705:Lignans; D016328:NF-kappa B; D010936:Plant Extracts; D044042:Receptors, Formyl Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003994:Bucladesine; D019950:Mitogen-Activated Protein Kinase 1; C054125:sesamin; D002118:Calcium