plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via toll-like receptor 4血浆蛋白在骨关节炎的滑液可以通过toll样受体刺激细胞因子生产4.pdfVIP

Sohn et al. Arthritis Research Therapy 2012, 14:R7 /content/14/1/R7 RESEARCH ARTICLE Open Access Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via Toll- like receptor 4 Dong Hyun Sohn1,2†, Jeremy Sokolove1,2†, Orr Sharpe1,2†, Jennifer C Erhart3,4, Piyanka E Chandra1,2, Lauren J Lahey1,2, Tamsin M Lindstrom1,2, Inyong Hwang1,2, Katherine A Boyer3,4, Thomas P Andriacchi3,4 and William H Robinson1,2* Abstract Introduction: Osteoarthritis (OA) is a degenerative disease characterized by cartilage breakdown in the synovial joints. The presence of low-grade inflammation in OA joints is receiving increasing attention, with synovitis shown to be present even in the early stages of the disease. How the synovial inflammation arises is unclear, but proteins in the synovial fluid of affected joints could conceivably contribute. We therefore surveyed the proteins present in OA synovial fluid and assessed their immunostimulatory properties. Methods: We used mass spectrometry to survey the proteins present in the synovial fluid of patients with knee OA. We used a multiplex bead-based immunoassay to measure levels of inflammatory cytokines in serum and synovial fluid from patients with knee OA and from patients with rheumatoid arthritis (RA), as well as in sera from healthy individuals. Significant differences in cytokine levels between groups were determined by significance analysis of microarrays, and relations were determined by unsupervised hierarchic clustering. To assess the immunostimulatory properties of a subset of the identified proteins, we tested the proteins’ ability to induce the production of inflammatory cytokines by macrophages. For proteins found to be stimulatory, the macrophage stimulation assays were repeated by using Toll-like receptor 4 (TLR4)-deficient macrop