Figure 2.

Role of TLRs in RA joint damage: initial cellular damage causes the release of DAMPs that are upregulated during inflammation, possibly caused by PAMPs.

Notes: Consequent TLR activation on cells residing in the synovium results in increased production of key inflammatory cytokines such as TNF-α and IL-1, which in turn can activate FLS, leading to increased MMPs. Increased MMPs lead to the loss of homeostasis between TIMPs and MMPs leading to increased destruction of ECM and cartilage, causing the release of DAMPs and activation of TLRs on FLS.

Abbreviations: DAMPs, damage-associated molecular patterns; ECM, extracellular matrix; FLS, fibroblast-like synoviocytes; HMGB-1, high-mobility group box 1; IL, interleukin; INF, interferon; miRNA, microRNA; MMPs, matrix metalloproteinases; PAMPs, pathogenic-associated molecular patterns; RA, rheumatoid arthritis; TIMPs, tissue inhibitor of metalloproteinases; TLR, toll-like receptor; TNF-α, tumor necrosis factor-α.