Bee venom and melittin reduce proinflammatory mediators in lipopolysaccharide-stimulated BV2 microglia.
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.
Moon
Dong-Oh
DO
Faculty of Applied Marine Science, Cheju National University, Jeju-si, Jeju Special Self-Governing Province 690-756, South Korea.
Park
Sung-Yong
SY
Lee
Kyeong-Jun
KJ
Heo
Moon-Soo
MS
Kim
Ki-Cheon
KC
Kim
Mun-Ock
MO
Lee
Jae-Dong
JD
Choi
Yung Hyun
YH
Kim
Gi-Young
GY
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
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