Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation
Tóm tắt
Chronic immune responses and inflammatory reactions in rheumatoid arthritis (RA) often cause severe destruction of cartilage and bone, but its mechanism is still a matter of controversy. We reported that interleukin-6 (IL-6) alone does not induce osteoclast formation, but soluble interleukin-6 receptors (sIL-6R) triggered the formation in the presence of IL-6 in cocultures of murine osteoblastic cells and bone marrow cells. In this study, we examined the involvement of sIL-6R and IL-6 in joint destruction in patients with RA. Although the frequency of patients having osteoclast-like multinucleated cells in synovium derived from the knee joint was not significantly different between RA (65%) and osteoarthritis (OA) patients (43%), the number of osteoclast-like cells found in the synovium was greater in the former than in the latter. Multinucleated cells obtained from RA synovium expressed the osteoclast-specific phenotype such as tartrate-resistant acid phosphatase, carbonic anhydrase II, vacuolar proton-ATPase and vitronectin receptors at similar levels to those from a human giant cell tumor of bone. The concentration of both IL-6 and sIL-6R was significantly higher in the synovial fluids from patients with RA than with OA. The concentration of IL-6 and sIL-6R correlated well with the roentgenologic grades of joint destruction. Dose-response curves for human IL-6 and human sIL-6R in inducing osteoclast-like cell formation in cocultures indicated that the RA synovial fluids contained sufficient IL-6 and sIL-6R to induce osteoclastogenesis. When synovial fluids from RA and OA patients were added to the cocultures, some of the RA synovial fluids containing high levels of IL-6 and sIL-6R stimulated osteoclast-like cell formation, which was strikingly inhibited by adding anti-IL-6R antibody simultaneously. These results suggest that IL-6 in the RA synovial fluids is at least in part responsible for joint destruction in the presence of sIL-6R through osteoclastogenesis.
Từ khóa
Tài liệu tham khảo
Zwaifler, 1988, New perspectives on the pathogenesis of rheumatoid arthritis, Am J Med, 85, 12, 10.1016/0002-9343(88)90356-7
Shimizu, 1985, Quantitative histologic studies on the pathogenesis of periarticular osteoporosis in rheumatoid arthritis, Arthr Rheum, 28, 25, 10.1002/art.1780280105
Miyasaka, 1988, Augmented interleukin-1 production and HLA-DR expression in the synovium of rheumatoid arthritis patients. Possible involvement in joint destruction, Arthr Rheum, 31, 480, 10.1002/art.1780310404
Hirano, 1989, Exsessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis, Eur J Immunol, 18, 1797, 10.1002/eji.1830181122
Miyasaka, 1989, Constitutive production of interleukin-6/B cell stimulatory factor-2 from inflammatory synovium, Clin Immunol Immunopathol, 52, 238, 10.1016/0090-1229(89)90175-X
Houssiau, 1988, Interleukin-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritises, Arthr Rheum, 31, 784, 10.1002/art.1780310614
Bhardwaj, 1989, IL-6/ IFN-β2 in synovial effusions of patients with rheumatoid arthritis and other arthritides, J Immunol, 143, 2153, 10.4049/jimmunol.143.7.2153
Ito, 1992, Effects of interleukin-6 on the metabolism of connective tissue components in rheumatoid synovial fibroblasts, Arthr Rheum, 35, 1197, 10.1002/art.1780351012
Dewhirst, 1985, Purification and partial sequence of human osteoclast-activation factor: identity with interleukin 1β, J Immunol, 135, 2565, 10.4049/jimmunol.135.4.2562
Sabatini, 1988, Infusions of recombinant human interleukins 1α and 1β cause hypercalcemia in normal mice, Proc Nail Acad Sci USA, 85, 5235, 10.1073/pnas.85.14.5235
Akatsu, 1991, Role of prostaglandins in interleukin-1-induced bone resorption in mice in vitro, J Bone Miner Res, 6, 183, 10.1002/jbmr.5650060212
Jilka, 1992, Increased osteoclast development after estrogen loss: mediation by interleukin-6, Science, 257, 88, 10.1126/science.1621100
Löwik, 1989, Parathyroid hormone (PTH) and PTH like protein (PLP) stimulate interleukin-6 production by osteogenetic cells: A possible role of interleukin-6 in ostcogenesis, Biochm Biophys Res Commun, 162, 1546, 10.1016/0006-291X(89)90851-6
Ishimi, 1990, IL-6 is produced by osteoblasts and induces bone resorption, J Immunol, 145, 3297, 10.4049/jimmunol.145.10.3297
Roodman, 1992, Perspectives Interlcukin-6: An osteotropic factor?, J Bone Miner Res, 7, 475, 10.1002/jbmr.5650070502
Al-Humidan, 1991, Interleukin-6 does not stimulate bone resorption in neonatal mouse calvariae, J Bone Miner Res, 6, 3, 10.1002/jbmr.5650060103
Barton, 1990, IL 3 and IL 6 do not induce bone resorption in vitro, Cytokine, 2, 217, 10.1016/1043-4666(90)90019-P
Taga, 1989, Interleukin-6 triggers the as sociation of its receptor with a possible signal transducer, gp130, Cell, 58, 573, 10.1016/0092-8674(89)90438-8
Saito, 1991, Preparation of soluble murine IL-6 receptor and anti-murine IL-6 receptor antibodies, J Immunol, 147, 168, 10.4049/jimmunol.147.1.168
Novick, 1989, Soluble cytokine receptors are present in normal human urine, J Exp Med, 170, 1409, 10.1084/jem.170.4.1409
Honda, 1992, Human soluble IL-6 receptor: Its detection and enhanced release by HIV infection, J Immunol, 148, 2175, 10.4049/jimmunol.148.7.2175
Gaillard, 1993, Increased and highly stable levels of functional soluble intcrleukin-6 receptor in sera of patients with monoclonal gammopathy, Eur J Immunol, 23, 820, 10.1002/eji.1830230408
Suzuki, 1993, Serum soluble interleukin-6 receptor in MRL/lpr mice is elevated with age and mediates the interleukin-6 signal, Eur J Immunol, 23, 1078, 10.1002/eji.1830230515
Benedetti, 1994, Serum soluble Interleukin 6 (IL-6) receptor and IL-6/soluble IL-6 receptor complex in systemic juvenile rheumatoid arthritis, J Clin Invest, 93, 2114, 10.1172/JCI117206
Suda, 1992, Modulation of osteoclast differentiation, Endocrine Rev, 13, 66
Takahashi, 1988, Osteoblastic cells are involved in osteoclast formation, Endocrinology, 123, 2600, 10.1210/endo-123-5-2600
Akatsu, 1992, Preparation and characterization of a mouse osteoclasl-like multinucleated cell population, J Bone Miner Res, 7, 1297, 10.1002/jbmr.5650071109
Tamura, 1993, Soluble interleukin-6 receptor triggers osteoclast formation by interleukin-6, Proc Nail Acad Sci USA, 90, 11924, 10.1073/pnas.90.24.11924
Ropes, 1958, 1958 Revision of diagnostic criteria for rheumatoid arthritis, Bull Rheum Dis, 9, 175
Larsen, 1977, Radiographic evaluation of rheumatoid arthritis and related conditions by standard reference films, Acta Radiologica Diagnosis, 18, 481, 10.1177/028418517701800415
Väänänen, 1984, Immunohistochemical localization of carbonic anhydrase isoenzymes I and II in human bone, cartilage and giant cell tumor, Histochemistry, 81, 485, 10.1007/BF00489754
Moriyama, 1989, Cold inactivation of vacuolar proton-ATPases, J Biol Chem, 264, 3577, 10.1016/S0021-9258(18)94105-0
Horton, 1985, Monoclonal antibodies to osteoclastomas (giant cell bone tomors): Definition of osteoclast-specific cellular antigens, Cancer Res, 45, 5663
Flanagan, 1992, An assessment of the ability of human bone marrow cultures to generate osteoelasts, Int J Exp Pathol, 73, 387
Ashton, 1993, Localisation of vitronectin receptor immunoreactivity and tartrate resistant acid phosphatase activity in synovium from patients with inflammatory or degenerative arthritis, Ann Rheum Dis, 52, 133, 10.1136/ard.52.2.133
Takahashi, 1991, Role of colony-stimulating factors in osteoclast development, J Bone Miner Res, 6, 977, 10.1002/jbmr.5650060912
Gravallese, 1993, Multinucleated cells in pigmented villonodular synovitis express an osteoelastic phenotype, Arthr Rheum., 36, S190
Kotake, 1992, Detection of myeloid precursors (granulocyte/macrophage colony forming units) in the bone marrow adjacent to rheumatoid arthritis joints, J Rheumatol, 19, 1511
Takahashi, 1988, Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures, Endocrinology, 122, 1373, 10.1210/endo-122-4-1373