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- W2317092757 abstract "Background Toll-like receptors (TLR) such as TLR7 and TLR9 that are activated by nucleic acids are known to be involved in the pathogenesis of systemic lupus erythematosus (SLE) while their role in the initiation and perpetuation of rheumatoid arthritis (RA) is unknown. To address this issue we applied oligonucleotides specifically antagonizing one or both TLRs in two different disease models: (i) pristane-induced arthritis (PIA) in DA rats which is driven by autoimmune processes induced by subcutaneous injection of the mineral oil pristane and (ii) the KRN serum transfer model in C57Bl/6 mice reflecting the late effector phase of erosive arthritis. In addition, involvement of TLR9 was also investigated in TLR9 knock-out mice. Objectives To investigate the role of TLR9 in the pathogenesis of autoimmune arthritis both in the early and in the effector disease phase. Methods Arthritis was induced in rats with the mineral oil pristane, in C57Bl/6 and TLR9 -/- mice by injection of KRN serum. Immunoregulatory oligodeoxynucleotide (ODN) sequences (IRS) antagonizing TLR7 or TLR9 were applied either subcutaneously (PIA) or intra-peritoneally (KRN). A non-inhibitory ODN was used as control and PBS served as placebo. Arthritis was scored using established scoring systems, inflammation and bone erosion were quantified by histology. Serum and cell culture cytokine levels were measured by ELISA. Results In the PIA model the TLR7 inhibitor and a TLR7/9 dual inhibitor showed no effect on arthritis development and severity. In contrast, arthritis severity was significantly reduced (p Conclusions TLR9 inhibition significantly reduced inflammation and bone erosion in PIA, but not in the KRN serum transfer model. These results suggest an important involvement of the DNA (CpG) recognizing TLR9 in the initiation of autoimmune arthritis whereas in the later disease phases TLR9 may even play a beneficial role similar to what has been found in models of SLE and other models for autoimmune diseases such as diabetes. Antagonizing TLR9 in human RA may therefore show beneficial effects only in the very earliest phase of the disease while its activation may have therapeutic effects in established disease. Disclosure of Interest None Declared" @default.
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- W2317092757 date "2013-06-01" @default.
- W2317092757 modified "2023-09-27" @default.
- W2317092757 title "THU0102 The Involvement of Toll-Like Receptor 9 in the Pathogenesis of Erosive Arthritis" @default.
- W2317092757 doi "https://doi.org/10.1136/annrheumdis-2013-eular.630" @default.
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