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Suppression of nitric oxide synthase by thienodolin in lipopolysaccharide-stimulated RAW 264.7 murine macrophage cells.
Park, Eun-Jung; Pezzuto, John M; Jang, Kyoung Hwa; Nam, Sang-Jip; Bucarey, Sergio A; Fenical, William.
Afiliación
  • Park EJ; College of Pharmacy, University of Hawaii at Hilo, Hilo, HI 96720-4019, USA.
Nat Prod Commun ; 7(6): 789-94, 2012 Jun.
Article en En | MEDLINE | ID: mdl-22816309
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lipopolisacáridos / Óxido Nítrico Sintasa / Macrófagos / Antiinflamatorios Límite: Animals Idioma: En Revista: Nat Prod Commun Asunto de la revista: BOTANICA / FARMACOLOGIA / QUIMICA Año: 2012 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lipopolisacáridos / Óxido Nítrico Sintasa / Macrófagos / Antiinflamatorios Límite: Animals Idioma: En Revista: Nat Prod Commun Asunto de la revista: BOTANICA / FARMACOLOGIA / QUIMICA Año: 2012 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos