The anti-inflammatory effects of platinum nanoparticles on the lipopolysaccharide-induced inflammatory response in RAW 264.7 macrophages

• Published in: Inflammation research Vol. 61; no. 11; pp. 1177 - 1185
• Main Authors: Rehman, Mati Ur, Yoshihisa, Yoko, Miyamoto, Yusei, Shimizu, Tadamichi
• Format: Journal Article
• Language: English
• Published: Basel SP Birkhäuser Verlag Basel 01-11-2012; Springer Nature B.V
• Subjects: AKT protein; Allergology; Animals; Anti-Inflammatory Agents - pharmacology; Antiinflammatory agents; Antitumor agents; Biomedical and Life Sciences; Biomedicine; Cell Line; Cell Survival - drug effects; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Cytokines - genetics; Cytokines - metabolism; Dermatology; Dinoprostone - metabolism; Extracellular signal-regulated kinase; Flow cytometry; Gene expression; Immunology; Inflammation; Inflammation - metabolism; Interleukin 6; Lipopolysaccharides; Macrophages; Metal Nanoparticles; Mice; Mitogen-Activated Protein Kinases - metabolism; nanoparticles; Neurology; NF-kappa B - metabolism; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Original Research Paper; Pharmacology/Toxicology; Phosphorylation; Platinum; Platinum - pharmacology; Prostaglandin E2; Proto-Oncogene Proteins c-akt - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; Rheumatology; RNA, Messenger - metabolism; Signal transduction; Tumor necrosis factor- alpha; Western blotting; Nuclear factor-kappa B; Reactive oxygen species; Platinum nanoparticles; Cyclooxygenase-2
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-012-0512-0

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.
Conclusion
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.