2007
DOI: 10.2353/ajpath.2007.060657
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The Toll-Like Receptor Adaptor Proteins MyD88 and Mal/TIRAP Contribute to the Inflammatory and Destructive Processes in a Human Model of Rheumatoid Arthritis

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Cited by 166 publications
(143 citation statements)
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“…Commensal microorganisms may also be involved in the development of autoimmune diseases, as suggested by the finding that some species of gut microbiota promote the pathogenesis of inflammatory bowel disease, especially Crohn's disease 36 Furthermore, human synovial membrane cultures from patients with rheumatoid arthritis were found to express TLR2 and TLR4 and to release endogenous TLR ligands which may contribute to destructive inflammation in the joints of these patients 59 . Finally, it has recently been shown that heterogeneous nuclear ribonucleoprotein (hbRNP), an RNA and DNA-binding protein that is a target of most nuclear antigen-specific T and B cells in systemic autoimmune diseases but also in human rheumatoid arthritis and in pristine-induced arthritis in rats, triggers TLR7-and TLR9-mediated activation of arthritogenic APCs, which activate pathogenic T cells 60 .…”
Section: The Link Between Pamps and Autoimmunitymentioning
confidence: 99%
“…Commensal microorganisms may also be involved in the development of autoimmune diseases, as suggested by the finding that some species of gut microbiota promote the pathogenesis of inflammatory bowel disease, especially Crohn's disease 36 Furthermore, human synovial membrane cultures from patients with rheumatoid arthritis were found to express TLR2 and TLR4 and to release endogenous TLR ligands which may contribute to destructive inflammation in the joints of these patients 59 . Finally, it has recently been shown that heterogeneous nuclear ribonucleoprotein (hbRNP), an RNA and DNA-binding protein that is a target of most nuclear antigen-specific T and B cells in systemic autoimmune diseases but also in human rheumatoid arthritis and in pristine-induced arthritis in rats, triggers TLR7-and TLR9-mediated activation of arthritogenic APCs, which activate pathogenic T cells 60 .…”
Section: The Link Between Pamps and Autoimmunitymentioning
confidence: 99%
“…However, the involvement of MMP-2 in the progression of the disease cannot be ruled out, since it is otherwise evident that MMP-2 up-regulation stimulated by TLRs pathways in synovial tissue modulates endothelial cells migration and new vessel formation, a pre-requisite for subsequent flogosis onset and joint destruction while the ECM degrading activity further promotes cartilage and bone breakdown (Saber et al, 2011;Sacre et al, 2007). Elevated levels of the enzyme are determined by cytokines stimulation of macrophages and, mainly, of synovial fibroblasts, the main source of the enzyme.…”
Section: Biological Aspectsmentioning
confidence: 99%
“…These include gp96, fibrinogen, Hsp60, Hsp70, hyaluronic acid, myeloid-related protein 8/14, and high mobility group box chromosomal protein 1 (26). Indeed, TLR inhibition by a dominant-negative form of the Toll/IL-1R domain containing adaptor protein molecules suppressed the spontaneous production of proinflammatory cytokines and MMPs from RSF (27). LPS was used as a TLR stimulator in this study.…”
Section: Inhibitory Effect Of Endogenous P16 Ink4a On Il-6 Productionmentioning
confidence: 99%