Induction of cyclooxygenase-2 in human synovial cells by β2-microglobulin

Background Prostaglandins (PGs) are important mediators of inflammation in arthritis. We evaluated the role of the cyclooxygenase-2 (COX-2) enzyme, which regulates PG biosynthesis, in osteoarthropathy associated with hemodialysis-associated amyloidosis (HAA) by characterizing COX-2 expression in beta 2-microglobulin-treated human synovial cells. Methods We examined the effects of alpha 2-microglobulin (beta(2)m), a major constituent protein of amyloid fibrils in HAA, on the COX-2 protein and mRNA expression in human synovial cells using Western blot and reverse transcriptase-polymerase chain reaction. Results. beta(2)m selectively increased the biosynthesis of COX-2 protein and induction of COX-2 mRNA in a dose-dependent manner. Immunoabsorption of beta(2)m-containing media by anti-beta(2)m-specific antibody abrogated beta(2)m-mediated COX-2 expression on synovial cells. On the other hand, dexamethasone markedly suppressed the induction of COX-2 protein and mRNA in beta(2)m-stimulated synovial cells. Conclusions. Our results suggest that induction of COX-2 expression by beta(2)m may be an important component of the inflammatory process in hemodialysis-associated osteoarthropathy.