Dipyrithione inhibits lipopolysaccharide-induced iNOS and COX-2 up-regulation in macrophages and protects against endotoxic shock in mice.

Abstract

Dipyrithione (PTS2) possesses anti-bacterial and anti-fungal activity. In the present study, we found that PTS2 dose-dependently inhibited the LPS-induced up-regulation of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein level in RAW264.7 cells. RT-PCR experiments showed that PTS2 suppressed LPS-induced iNOS but not COX-2 expression at the mRNA level. As expected, PTS2 prevented NO secretion in RAW264.7 cells. Furthermore, PTS2 administration significantly decreased LPS-induced mortality in mice. Mechanistically, PTS2 decreased expression and phosphorylation of STAT1, but did not interfere with the MAPK and NF-kappaB pathways. In conclusion, PTS2 protects mice against endotoxic shock and inhibits LPS-induced production of pro-inflammatory mediators, suggesting that PTS2 could play an anti-inflammatory role in response to LPS.

• Authors: Ziwen Liu, Yumei Fan, Yu Wang, Cui Han, Yu Pan, Huang Huang, Ying Ye, Lan Luo, Zhimin Yin
• Journal: FEBS letters (FEBS Lett) Vol. 582 Issue 12 Pg. 1643-50 (May 28 2008) ISSN: 0014-5793 [Print] England
• PMID: 18435922 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cyclooxygenase 2 Inhibitors
• Lipopolysaccharides
• NF-kappa B
• Pyridines
• STAT1 Transcription Factor
• Nitric Oxide
• dipyrithione
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Mitogen-Activated Protein Kinase Kinases

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Cell Line
• Cyclooxygenase 2 (drug effects)
• Cyclooxygenase 2 Inhibitors (pharmacology, therapeutic use)
• Lipopolysaccharides (toxicity)
• Macrophages (drug effects, enzymology)
• Male
• Mice
• Mice, Inbred ICR
• Mitogen-Activated Protein Kinase Kinases (metabolism)
• NF-kappa B (metabolism)
• Nitric Oxide (antagonists & inhibitors, biosynthesis)
• Nitric Oxide Synthase Type II (antagonists & inhibitors)
• Phosphorylation (drug effects)
• Pyridines (pharmacology, therapeutic use)
• STAT1 Transcription Factor (metabolism)
• Shock, Septic (prevention & control)
• Up-Regulation