title: Investigating the Role of Toll-Like Receptors in Models of Arthritis.
abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation leading to tissue destruction and progressive loss of joint function. Here we describe two methods that can be used to assess the contribution of toll-like receptors (TLRs), and their potential ligands, to RA pathogenesis. We focus on the antigen-induced model of murine arthritis and human synovial tissue explant models. Both enable detection of TLR, and TLR ligand, expression, as well as investigation of the effect of inhibition of these molecules. Each offers a unique insight into disease; with murine models allowing kinetic analysis in live animals and explant models allowing examination of inflamed human tissue, which together can help us to dissect the role of TLRs in the onset and progression of RA.
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Roosevelt Drive, Oxford, OX3 7FY, UK.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Piccinini
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Roosevelt Drive, Oxford, OX3 7FY, UK.
authors.forename: Lynn
authors.initials: L
authors.lastname: Williams
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Roosevelt Drive, Oxford, OX3 7FY, UK.
authors.forename: Fiona E
authors.initials: FE
authors.lastname: McCann
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Roosevelt Drive, Oxford, OX3 7FY, UK. kim.midwood@kennedy.ox.ac.uk.
authors.forename: Kim S
authors.initials: KS
authors.lastname: Midwood
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000378:metabolism*; D018929:Cell Culture Techniques; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000941:Antigens; D016207:Cytokines; D051193:Toll-Like Receptors
keywords: Antigen-induced arthritis; DAMPs; Endogenous ligands; Human synovial tissue; Rheumatoid arthritis; Sterile inflammation; Toll-like receptor