Anti-inflammatory effects of beta-lapachone in lipopolysaccharide-stimulated BV2 microglia.
beta-Lapachone (LAPA) is a chemotherapeutic agent that can inhibit the expression of nitric oxide (NO) and inducible NO synthase (iNOS) in alveolar macrophages. No other information on the agent's anti-inflammatory activity has been reported. In the present study, we investigated the molecular mechanism of LAPA on lipopolysaccharide (LPS)-induced responses in BV2 microglia. Treatment of LAPA significantly inhibited NO and PGE(2) release in LPS-stimulated BV2 microglia. The inhibition of iNOS and COX-2 was also observed, suggesting the blockage of transcriptional levels. In addition, LAPA attenuated the expression of mRNA and proteins of proinflammatory cytokines, such as interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha in a dose-dependent manner. Moreover, LAPA exhibits anti-inflammatory properties by suppressing the NF-kappaB activation by blocking IkappaBalpha degradation and downregulating the ERK, p38 mitogen-activated protein kinase (MAPK) and Akt pathway. The results show that LAPA may be useful as a potential anti-inflammatory agent for attenuating inflammatory diseases.
Moon
Dong-Oh
DO
Faculty of Applied Marine Science, Cheju National University, Jeju, South Korea.
Choi
Yung Hyun
YH
Kim
Nam-Duk
ND
Park
Yeong-Min
YM
Kim
Gi-Young
GY
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D008070:Lipopolysaccharides; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009285:Naphthoquinones; D009569:Nitric Oxide; C014638:beta-lapachone; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D017346:Protein Serine-Threonine Kinases; D015232:Dinoprostone