Induction of cyclooxygenase-2 in human synovial cells by beta 2-microglobulin.

Abstract

Prostaglandins (PGs) are important mediators of inflammation in arthritis. We evaluated the role of the cycloxygenase-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. We examined the effects of beta 2-microglobulin (beta 2m), 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. beta 2m selectively increased the biosynthesis of COX-2 protein and induction of COX-2 mRNA in a dose-dependent manner. Immunoabsorption of beta 2m-containing media by anti-beta 2m-specific antibody abrogated beta 2m-mediated COX-2 expression on synovial cells. On the other hand, dexamethasone markedly suppressed the induction of COX-2 protein and mRNA in beta 2m-stimulated synovial cells. Our results suggest that induction of COX-2 expression by beta 2m may be an important component of the inflammatory process in hemodialysis-associated osteoarthropathy.