title: Bee venom and melittin reduce proinflammatory mediators in lipopolysaccharide-stimulated BV2 microglia.
abstract: Bee venom (BV), well known as a traditional Oriental medicine, has been shown to exhibit anti-arthritic and anti-carcinogenic effects. However, the molecular mechanisms responsible for the anti-inflammatory activity of BV have not been elucidated in microglia. In the present study, we investigated the anti-inflammatory effect of BV and its major component, melittin (MEL), on lipopolysaccharide (LPS)-stimulated BV2 microglia. Our results indicate that BV and MEL suppress LPS-induced nitric oxide (NO) and inducible NO synthase (iNOS) expression in a dose-dependent manner, without causing cytotoxicity in BV2 microglia. Moreover, BV and MEL suppressed LPS-induced activation of nuclear factor kappa B (NF-kappaB) by blocking degradation of IkappaBalpha and phosphorylation of c-Jun N-terminal kinase (JNK) and Akt, which resulted in inhibition of iNOS expression. Our data also indicate that BV and MEL exert anti-inflammatory effects by suppressing the transcription of cyclooxygenase (COX)-2 genes and proinflammatory cytokines, such as interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha. BV and MEL also attenuated the production of prostaglandin E(2) (PGE(2)). These results demonstrate that BV and MEL possess a potent suppressive effect on proinflammatory responses of BV2 microglia and suggest that these compounds may offer substantial therapeutic potential for treatment of neurodegenerative diseases that are accompanied by microglial activation.
authors.affiliation: Faculty of Applied Marine Science, Cheju National University, Jeju-si, Jeju Special Self-Governing Province 690-756, South Korea.
authors.forename: Dong-Oh
authors.initials: DO
authors.lastname: Moon
authors.forename: Sung-Yong
authors.initials: SY
authors.lastname: Park
authors.forename: Kyeong-Jun
authors.initials: KJ
authors.lastname: Lee
authors.forename: Moon-Soo
authors.initials: MS
authors.lastname: Heo
authors.forename: Ki-Cheon
authors.initials: KC
authors.lastname: Kim
authors.forename: Mun-Ock
authors.initials: MO
authors.lastname: Kim
authors.forename: Jae-Dong
authors.initials: JD
authors.lastname: Lee
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001514:Bee Venoms / Q000737:chemistry / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D051550:I-kappa B Kinase / Q000378:metabolism; D015151:Immunoblotting; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008555:Melitten / Q000737:chemistry / Q000494:pharmacology*; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D001514:Bee Venoms; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; D008555:Melitten; D009569:Nitric Oxide; D011392:Proline; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase; D048031:JNK Mitogen-Activated Protein Kinases; D015232:Dinoprostone