title: The anti-inflammatory effects of platinum nanoparticles on the lipopolysaccharide-induced inflammatory response in RAW 264.7 macrophages.
abstract: OBJECTIVE
  Platinum nanoparticles (nano-Pt) have been reported to possess anti-oxidant and anti-tumor activities. However, the biological activity and mechanism of action of nano-Pt in inflammation are still unknown. The present study was designed to determine the in-vitro anti-inflammatory effects of nano-Pt on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells.
  
  
  METHODS
  RAW 264.7 macrophages were used for the study. The LPS-induced production of reactive oxygen species (ROS) was determined by flow cytometry. The prostaglandin E(2) (PGE(2)) concentration was measured using a PGE(2) assay kit. The protein levels and mRNA expression of the pro-inflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-1β and IL-6], along with cyclooxygenase (COX-2) and inducible nitric oxide synthase, were analyzed by Western blotting and reverse transcription-polymerase chain reaction analysis. The phosphorylation of extracellular signal regulated kinase (ERK1/2) and Akt, and the phosphorylation and degradation of inhibitory kappa B-alpha (IκB-α) was determined by Western blot analysis.
  
  
  RESULTS
  Nano-Pt significantly reduced the LPS-induced production of intracellular ROS and inflammatory mediators. In addition, nano-Pt suppressed the phosphorylation of ERK1/2 and Akt, and significantly inhibited the phosphorylation/degradation of IκB-α as well as nuclear factor kappa-B (NFκB) transcriptional activity.
  
  
  CONCLUSIONS
  These results suggest that the anti-inflammatory properties of nano-Pt may be attributed to their downregulation of the NFκB signaling pathway in macrophages, thus supporting the use of nano-Pt as an anti-inflammatory agent.
authors: Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan.
authors: Mati Ur
authors: MU
authors: Rehman
authors: Yoko
authors: Y
authors: Yoshihisa
authors: Yusei
authors: Y
authors: Miyamoto
authors: Tadamichi
authors: T
authors: Shimizu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides; D053768:Metal Nanoparticles; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010984:Platinum / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D010984:Platinum; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone