%0 Journal Article
%T PDE4 inhibitor rolipram inhibits the expression of microsomal prostaglandin E synthase©\1 by a mechanism dependent on MAP kinase phosphatase©\1
%A Eeva Moilanen
%A Lauri Tuure
%A Mari H£¿m£¿l£¿inen
%J Archive of "Pharmacology Research & Perspectives".
%D 2017
%R 10.1002/prp2.363
%X Phosphodiesterase©\4 (PDE4) inhibitors have recently been introduced to the treatment of COPD and psoriatic arthritis. Microsomal prostaglandin E synthase©\1 (mPGES©\1) is an inducible enzyme synthesizing PGE 2, the most abundant prostanoid related to inflammation and inflammatory pain. mPGES©\1 is a potential drug target for novel anti©\inflammatory treatments aiming at an improved safety profile as compared to NSAIDs. Here we investigated the effect of the PDE4 inhibitor rolipram on the expression of mPGES©\1 in macrophages; and a potential mediator role in the process for MAP kinase phosphatase©\1 (MKP©\1) which is an endogenous factor limiting the activity of the proinflammatory MAP kinases p38 and JNK. The expression of mPGES©\1 was decreased, whereas that of MKP©\1 was enhanced by rolipram in wild©\type murine macrophages. Interestingly, rolipram did not reduce mPGES©\1 expression in peritoneal macrophages from MKP©\1©\deficient mice. A reduced phosphorylation of JNK, but not p38 MAP kinase, was specifically associated with the decreased expression of mPGES©\1. Accordingly, mPGES©\1 expression was suppressed by JNK but not p38 inhibitor. These findings underline the significance of the increased MKP©\1 expression and decreased JNK phosphorylation associated with the downregulated expression of mPGES©\1 by PDE4 inhibitors in inflammation
%K MAP kinases
%K MKP©\1
%K mPGES©\1
%K PDE4
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723697/