Microsomal prostaglandin E synthase-1 (mPGES-1) catalyses the formation of PGE
Primary human chondrocytes were isolated from cartilage samples obtained from osteoarthritis (OA) patients undergoing knee replacement surgery. Primary mouse chondrocytes were isolated from cartilage samples of MKP-1 deficient (knock-out, KO) and corresponding wild type (WT) mice. Expression of mPGES-1 and MKP-1 were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot, and MAP kinase phosphorylation by Western blot.
Dexamethasone inhibited the expression of mPGES-1 in primary human chondrocytes and in chondrocytes from wild type but not from MKP-1 deficient mice. Dexamethasone enhanced MKP-1 expression in chondrocytes from wild type mice as well as in primary human OA chondrocytes. Dexamethasone induced the dephosphorylation of both p38 and JNK, whereas mPGES-1 expression was downregulated by selective inhibitors of p38 only.
The results show that MKP-1 is a crucial mediator of pharmacological control of inflammatory mPGES-1 expression by glucocorticoids, and underline MKP-1 as a potential anti-inflammatory drug target.