Attenuation of the acute inflammatory response by dual specificity phosphatase 1 by inhibition of p38 MAP kinase

作者：Korhonen Riku^*; Turpeinen Tuija; Taimi Ville; Nieminen Riina; Goulas Antonis; Moilanen Eeva

来源：Molecular Immunology, 2011, 48(15-16): 2059-2068.

DOI：10.1016/j.molimm.2011.06.439

• DUSP1
• p38 MAPK
• TNF
• IL-6
• COX2
• Macrophages
• Carrageenan paw edema

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, tumornecrosis 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.

• 出版日期2011-9