title: Suppression of nitric oxide synthase by thienodolin in lipopolysaccharide-stimulated RAW 264.7 murine macrophage cells.
abstract: The measurement of nitric oxide in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells is used as a model for evaluating the anti-inflammatory or chemopreventive potential of substances. Thienodolin, isolated from a Streptomyces sp. derived from Chilean marine sediment, inhibited nitric oxide production in LPS-stimulated RAW 264.7 cells (IC50 = 17.2 +/- 1.2 microM). At both the mRNA and protein levels, inducible nitric oxide synthase (iNOS) was suppressed in a dose-dependent manner. Mitogen-activated protein kinases (MAPKs), one major upstream signaling pathway involved in the transcription of iNOS, were not affected by treatment of thienodolin. However, the compound blocked the degradation of IkappaBa resulting in inhibition of NF-kappaB p65 nuclear translocation, and inhibited the phosphorylation of signal transducers and activators of transcription 1 (STAT1) at Tyr701. This study supports further exploration of thienodolin as a potential therapeutic agent with a unique mechanistic activity.
authors: College of Pharmacy, University of Hawaii at Hilo, Hilo, HI 96720-4019, USA.
authors: Eun-Jung
authors: EJ
authors: Park
authors: John M
authors: JM
authors: Pezzuto
authors: Kyoung Hwa
authors: KH
authors: Jang
authors: Sang-Jip
authors: SJ
authors: Nam
authors: Sergio A
authors: SA
authors: Bucarey
authors: William
authors: W
authors: Fenical
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D019001:Nitric Oxide Synthase; D020928:Mitogen-Activated Protein Kinases