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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
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Cell Line
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Cyclooxygenase 2 / drug effects*
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Cyclooxygenase 2 Inhibitors / pharmacology*
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Cyclooxygenase 2 Inhibitors / therapeutic use
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Lipopolysaccharides / toxicity
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Macrophages / drug effects
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Macrophages / enzymology
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Male
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Mice
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Mice, Inbred ICR
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Mitogen-Activated Protein Kinase Kinases / metabolism
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NF-kappa B / metabolism
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Nitric Oxide / antagonists & inhibitors
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Nitric Oxide / biosynthesis
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Nitric Oxide Synthase Type II / antagonists & inhibitors*
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Phosphorylation / drug effects
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Pyridines / pharmacology*
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Pyridines / therapeutic use
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STAT1 Transcription Factor / metabolism
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Shock, Septic / prevention & control*
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Up-Regulation
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Cyclooxygenase 2 Inhibitors
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Lipopolysaccharides
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NF-kappa B
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Pyridines
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STAT1 Transcription Factor
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Nitric Oxide
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dipyrithione
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Nitric Oxide Synthase Type II
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Cyclooxygenase 2
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Mitogen-Activated Protein Kinase Kinases