title: Indirubin-3-monoxime exhibits anti-inflammatory properties by down-regulating NF-κB and JNK signaling pathways in lipopolysaccharide-treated RAW264.7 cells.
abstract: OBJECTIVE
  Indirubin-3-monoxime (I3M), an indirubin analogue that shows favorable inhibitory activity targeting cyclin-dependent kinase and glycogen synthase kinase, exhibits various biological properties, including chemopreventive, antiangiogenic, and neuropreventive activities. In the present study, we investigated the ability of I3M to regulate inflammatory reactions in macrophages.
  
  
  METHODS
  The effects of I3M on inflammation, lipopolysaccharide (LPS)-induced releases of inflammatory mediators, nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling was examined by ELISA and Western blotting analysis.
  
  
  RESULTS
  I3M suppressed not only the generation of nitric oxide (NO) and prostaglandin E(2) but also the expression of inducible NO synthase and cyclooxygenase-2 induced by LPS. Similarly, I3M inhibited the release of pro-inflammatory cytokines induced by LPS in RAW264.7 cells, including interleukin (IL)-1β and IL-6. The underlying mechanism of I3M on anti-inflammatory action was correlated with down-regulation of the NF-κB and MAPK activation.
  
  
  CONCLUSIONS
  Our data collectively indicate that I3M inhibited the production of several inflammatory mediators and might be used for the treatment of various inflammatory diseases.
authors.affiliation: Department of Biomedical Science, College of Natural Science, Catholic University of Daegu, 330 Geumrak-Ri, Gyeoungsan-Si 700-712, Korea. toto0818@cu.ac.kr
authors.forename: Jin-Kyung
authors.initials: JK
authors.lastname: Kim
authors.forename: Geun-Mook
authors.initials: GM
authors.lastname: Park
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics; D015232:Dinoprostone / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D009573:Nitrites / Q000378:metabolism; D010091:Oximes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D007211:Indoles; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; D010091:Oximes; D012333:RNA, Messenger; C474021:indirubin-3'-monoxime; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone