Beta 2-microglobulin induces stromelysin production by human synovial fibroblasts.
beta 2-Microglobulin (beta 2-m) is a major constituent of amyloid fibrils in hemodialysis-associated amyloidosis (HAA), a serious complication in patients on long-term hemodialysis. The most distinctive pathological feature of HAA is the deposition of amyloid fibrils with subsequent articular inflammation and destruction. However, the pathological role of beta 2-m is not well known at present. We investigated the effects of beta 2-m on the production of proteinases from synovial fibroblasts isolated from patients with rheumatoid arthritis. beta 2-m stimulated synovial fibroblasts to produce stromelysin, a neutral matrix metalloproteinase (MMP-3). The production of MMP-2 and of a tissue inhibitor of metalloproteinase-1 (TIMP-1) were not enhanced by beta 2-m-treated synovial fibroblasts. Stromelysin is capable of degrading several components of the extracellular matrix and believed to be the key enzyme causing articular destruction in inflammatory joint diseases. Our results suggest a novel role for beta 2-m in articular inflammation and destruction mediated by stromelysin in HAA.
Migita
K
K
The First Department of Internal Medicine, Nagasaki University School of Medicine, Japan. eguchi@net.nagasaki-u.ac.jp
Eguchi
K
K
Tominaga
M
M
Origuchi
T
T
Kawabe
Y
Y
Nagataki
S
S
D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D018093:Gelatinases / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000187:drug effects; D008666:Metalloendopeptidases / Q000096:biosynthesis; D008934:Mitogens / Q000494:pharmacology; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D001613:beta 2-Microglobulin / Q000494:pharmacology*
D007375:Interleukin-1; D008934:Mitogens; D014409:Tumor Necrosis Factor-alpha; D001613:beta 2-Microglobulin; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D013936:Thymidine