TY - JOUR
T1 - The anti-inflammatory effects of platinum nanoparticles on the lipopolysaccharide-induced inflammatory response in RAW 264.7 macrophages
AU - Rehman, Mati Ur
AU - Yoshihisa, Yoko
AU - Miyamoto, Yusei
AU - Shimizu, Tadamichi
N1 - Funding Information:
Acknowledgments This research was supported by a Grant-in-Aid for Scientific Research (No. 20591337) from the Japan Society for the Promotion of Science.
PY - 2012/11
Y1 - 2012/11
N2 - 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 E2 (PGE2) concentration was measured using a PGE2 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.
AB - 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 E2 (PGE2) concentration was measured using a PGE2 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.
KW - Cyclooxygenase-2
KW - Nuclear factor-kappa B
KW - Platinum nanoparticles
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=84868140136&partnerID=8YFLogxK
U2 - 10.1007/s00011-012-0512-0
DO - 10.1007/s00011-012-0512-0
M3 - 学術論文
C2 - 22752115
AN - SCOPUS:84868140136
SN - 1023-3830
VL - 61
SP - 1177
EP - 1185
JO - Inflammation Research
JF - Inflammation Research
IS - 11
ER -