Dual specificity phosphatase 1 (DUSP1) dephosphorylates and, hence, regulates 
the activity of MAP kinases. The present study investigated the effect of DUSP1 
on inflammatory gene expression and on the development of carrageenan-induced 
inflammation. It was found that DUSP1 expression was increased by LPS, and the 
down-regulation of DUSP1 by siRNA enhanced the phosphorylation of p38 MAPK, 
while JNK phosphorylation was not affected in murine macrophages. LPS-induced 
interleukin (IL)-6, tumor-necrosis factor (TNF) and cyclooxygenase-2 (COX2) 
expression were enhanced in bone marrow-derived macrophages (BMMs) from 
DUSP1(-/-) mice as compared to those from wild-type mice. In addition, 
down-regulation of DUSP1 by siRNA enhanced IL-6, TNF and COX2 expression in J774 
macrophages, while p38 MAPK inhibitors SB202190 and BIRB 796 inhibited the 
expression of those inflammatory factors. In vivo, the intensity of the 
carrageenan-induced paw edema reaction was increased in DUSP1(-/-) mice as 
compared to the wild-type animals. In conclusion, DUSP1 is an important negative 
regulator of the acute inflammatory response by limiting p38 MAPK, and compounds 
which enhance DUSP1 expression or activity may hold a promise as 
anti-inflammatory drugs.