The role of Toll-like receptor signalling in the pathogenesis of arthritis

Pre–B cell colony‐enhancing factor/visfatin, a new marker of inflammation in rheumatoid arthritis with proinflammatory and matrix‐degrading activities

“…TLRs were shown to be key players in inflammatory and destructive processes in RA (3,4,20,25). TLR ligands of microbial origin as well as endogenous TLR ligands were demonstrated to be present in RA synovial fluid as possible drivers of inflammatory processes (1,26). Our findings suggest that the stimulation of RASFs by TLR ligands is at least partially dependent on PBEF expression.…”

“…Synovial fibroblasts (SFs) and inflammatory cells such as macrophages and T cells play key roles in this process. There is mounting evidence for an important function of innate immunity in the pathogenesis of RA (1). Activation of cells by microbial components and also by endogenous molecules via pattern recognition receptors, such as Toll-like receptors (TLRs), results in the production of a variety of cytokines, chemokines, and matrix metalloproteinases (MMPs), some of which are characteristically observed in patients with RA (2).…”

Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis

“…To confirm the stimulatory effect of TNF␣ on miR-155 expression and to further investigate the regulation of miR-155 by other proinflammatory mediators known to be critically involved in the development of inflammation and destruction of the rheumatoid joints, we stimulated RASFs with TNF␣, IL-1␤, and TLR ligands (26) and measured miR-155 levels by semiquantitative TaqMan miRNA assay. We found that, similar to the stimulatory effects of TNF␣, IL-1␤ as well as the TLR ligands LPS, poly(I-C), and bLP markedly induced miR-155 expression in RASFs after 8 hours of stimula-tion (n ϭ 6) ( Figure 1A).…”

Increased macrophage activation mediated through toll‐like receptors in rheumatoid arthritis

“…The presence of activated T cells and B cells, the rearrangement of their respective receptors, and their specificity for local antigens within the joint all support the role of the antigen-driven adaptive responses in the pathogenesis of RA (1). However, an increasing body of data supports the role of the innate immune system in RA and in experimental models of RA (2)(3)(4). Toll-like receptors (TLRs) may be critical for the generation of both innate and adaptive immunity.…”

“…This activation promotes the development of the adaptive immune response involving T and B lymphocytes, which then contributes to clearance of the pathogenic stimulus and resolution of the inflammatory response. Despite the development of an adaptive immune response, expression of the early responders TNF␣ and IL-1␤ persists and may directly contribute to the pathogenesis of RA (2,(4)(5)(6)(7)(8).…”