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Dipyrithione inhibits lipopolysaccharide‐induced iNOS and COX‐2 up‐regulation in macrophages and protects against endotoxic shock in mice
Author(s) -
Liu Ziwen,
Fan Yumei,
Wang Yu,
Han Cui,
Pan Yu,
Huang Huang,
Ye Ying,
Luo Lan,
Yin Zhimin
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.04.016
Subject(s) - lipopolysaccharide , nitric oxide synthase , nitric oxide , chemistry , cyclooxygenase , secretion , phosphorylation , enzyme , endotoxic shock , mapk/erk pathway , messenger rna , pharmacology , biochemistry , biology , immunology , gene , organic chemistry
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‐κB 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.