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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Migita
K
K
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan. eguchi@net.nagasaki-u.ac.jp
Tominaga
M
M
Origuchi
T
T
Kawabe
Y
Y
Aoyagi
T
T
Urayama
S
S
Yamasaki
S
S
Hida
A
A
Kawakami
A
A
Eguchi
K
K
D015153:Blotting, Western; D051546:Cyclooxygenase 2; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D001613:beta 2-Microglobulin / Q000494:pharmacology*