Selenoorganic compound, ebselen, inhibits nitric oxide and tumor necrosis factor-alpha production by the modulation of jun-N-terminal kinase and the NF-kappab signaling pathway in rat Kupffer cells.

In response to the bacterial endotoxin, LPS, Kupffer cells are induced to express NO and TNF-alpha. These compounds are involved in hepatic inflammation/injury, especially that associated with endotoxic shock. In this study, we demonstrate that ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]one), a selenoorganic compound, blocks LPS-induced NO and TNF-alpha production by cultured rat liver Kupffer cells. LPS can activate both the NF-kappaB signaling pathway and MAPK signal transduction pathways such as JNK and p38 MAPK. We find that ebselen inhibits LPS-induced NF-kappaB nuclear translocalization, and also suppresses the LPS-induced phosphorylation of JNK, but not the phosphorylation of p38 MAPK. This inhibition of signal transduction leads to a decrease in the transcription of TNF-alpha and the inducible isoform of NO. Furthermore, ebselen inhibits LPS-induced COX-2 expression, which is responsible for proinflammatory prostaglandin production, without affecting constitutive COX-1 expression. These data suggest the mechanism by which ebselen acts as an antiinflammatory agent, and also suggest that ebselen may be potent in preventing hepatic injury such as endotoxic shock, in which Kupffer cell activation has been implicated.

Shimohashi N ，Nakamuta M ，Uchimura K ，Sugimoto R ，Iwamoto H ，Enjoji M ，Nawata H ... -  《JOURNAL OF CELLULAR BIOCHEMISTRY》

AgC10, a mucin from Trypanosoma cruzi, destabilizes TNF and cyclooxygenase-2 mRNA by inhibiting mitogen-activated protein kinase p38.

Alcaide P ，Fresno M 《EUROPEAN JOURNAL OF IMMUNOLOGY》

Caffeic acid phenethyl ester protects mice from lethal endotoxin shock and inhibits lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW 264.7 macrophages via the p38/ERK and NF-kappaB pathways.

Jung WK ，Choi I ，Lee DY ，Yea SS ，Choi YH ，Kim MM ，Park SG ，Seo SK ，Lee SW ，Lee CM ，Park YM ，Choi IW ... -  《INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY》

Prostaglandin E2 affects differently the release of inflammatory mediators from resident macrophages by LPS and muramyl tripeptides.

Dieter P ，Hempel U ，Kamionka S ，Kolada A ，Malessa B ，Fitzke E ，Tran-Thi TA ... -  《MEDIATORS OF INFLAMMATION》

Dipyridamole activation of mitogen-activated protein kinase phosphatase-1 mediates inhibition of lipopolysaccharide-induced cyclooxygenase-2 expression in RAW 264.7 cells.

Chen TH ，Kao YC ，Chen BC ，Chen CH ，Chan P ，Lee HM ... -  《EUROPEAN JOURNAL OF PHARMACOLOGY》