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Microsomal Prostaglandin E Synthase‐1, Ephrins, and Ephrin Kinases as Suspected Therapeutic Targets in Arthritis
Author(s) -
ROMANOVSKY ANDREJ A.,
IVANOV ANDREI I.,
PETERSEN SCOTT R.
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1351.016
Subject(s) - ephrin , kinase , arthritis , chemistry , atp synthase , medicine , pharmacology , receptor , biochemistry , enzyme
Feeding information obtained in one criminal case into the profile of another crime often helps to solve the latter. The literature on two different “crimes,” namely, acute systemic inflammation and arthritis (including osteoarthritis [OA] and rheumatoid arthritis [RA] deals largely with the same “gang” of inflammatory mediators, such as prostaglandin (PG) E 2 . Early investigations suggested that microsomal PGE synthase‐1 (mPGES‐1; a terminal PGE 2 ‐synthesizing enzyme) plays a pivotal role in bacterial lipopolysaccharide (LPS)‐induced systemic inflammation, but overlooked the possibility that the same enzyme could be involved in OA or RA. Later studies showed that mPGES‐1 is indeed a key perpetrator in arthritic diseases, a fact that could have been predicted earlier by pooling the new knowledge about mPGES‐1 into the profile of arthritic diseases. In this review, we analyze our recent study on the expression of erythropoietin‐producing hepatocellular (Eph) receptor kinases and their ligands, ephrins, in LPS‐induced systemic inflammation. By pooling these results together with literature data into the profile of RA, we conclude that Eph kinases and ephrins are prime suspects for being involved in the pathogenesis of RA. We further conjecture that the involvement of Eph kinases and ephrins may be realized via the induction of angiogenesis in the inflamed joint, promotion of leukocyte infiltration, and activation of the infiltrated cells. Studies to test this new hypothesis seem warranted, and our prediction is that the “smoking gun” will be found.