title: A disintegrin and metalloprotease-10 is correlated with disease activity and mediates monocyte migration and adhesion in rheumatoid arthritis.
abstract: A disintegrin and metalloproteases (ADAMs) are a family of proteins that have been reported to be involved in several inflammatory conditions. We examined the secretion of ADAM-10 in biological fluids from patients with rheumatoid arthritis (RA) and the role it plays in monocyte migration. ADAM-10 levels were measured using enzyme-linked immunosorbent assays and immunofluorescence. To examine the role of ADAM-10 in RA synovial fluids (SFs), we studied THP-1 (human acute monocyte leukemia cell line) and monocyte chemotaxis. To determine whether ADAM-10 plays a role in cell proliferation in the RA synovium, we assayed the proliferation of ADAM-10 small interfering RNA (siRNA)-transfected RA fibroblast-like synoviocytes (FLSs). The ADAM-10 level in RA serum was significantly higher than that in normal serum and was correlated with a disease activity score of 28. ADAM-10-depleted RA SFs showed a decrease in THP-1 and monocyte migratory activity compared with that of sham-depleted controls. ADAM-10 siRNA inhibited monocyte adhesion to RA FLSs. Finally, blocking ADAM-10 secretion in RA FLSs resulted in decreased production of fractalkine/CX3CL1 and vascular endothelial cell growth factor. These data indicate that ADAM-10 plays a role in monocyte migration in RA and suggest that targeting ADAM-10 may provide a method of decreasing inflammation and potentially treating other inflammatory diseases.
authors: Department of Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan. Electronic address: t.isozaki@med.showa-u.ac.jp.
authors: Takeo
authors: T
authors: Isozaki
authors: Department of Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors: Sho
authors: S
authors: Ishii
authors: Department of Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors: Shinichiro
authors: S
authors: Nishimi
authors: Department of Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors: Airi
authors: A
authors: Nishimi
authors: Department of Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors: Nao
authors: N
authors: Oguro
authors: Department of Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors: Shinya
authors: S
authors: Seki
authors: Department of Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors: Yoko
authors: Y
authors: Miura
authors: Department of Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors: Yusuke
authors: Y
authors: Miwa
authors: Department of Orthopedics, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors: Koei
authors: K
authors: Oh
authors: Department of Orthopedics, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors: Yoichiro
authors: Y
authors: Toyoshima
authors: Department of Orthopedics, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors: Masanori
authors: M
authors: Nakamura
authors: Department of Orthopedics, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors: Katsunori
authors: K
authors: Inagaki
authors: Department of Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors: Tsuyoshi
authors: T
authors: Kasama
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000473:pathology*; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D002633:Chemotaxis; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008565:Membrane Proteins / Q000097:blood*; D009000:Monocytes / Q000473:pathology*; D034741:RNA, Small Interfering / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human