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• W2149641211 abstract "Toll-like receptor 9 (TLR-9), a receptor for CpG DNA, has been implicated in the activation of immune cells in lupus. We undertook this study to determine whether the expression of TLR-9 in resident renal cells in lupus nephritis is related to the development of tubulointerstitial injury.TLR-9 was analyzed in selectively retrieved renal tissue from (NZB x NZW)F1 mice at different stages of disease by laser capture microdissection combined with real-time quantitative reverse transcriptase-polymerase chain reaction, and in renal biopsy specimens from lupus nephritis patients by immunohistochemistry. We investigated for the molecular component responsible for TLR-9 activation by cultured proximal tubular cells in serum from patients with lupus.Renal tissue from NZB x NZW mice displayed robust TLR-9 expression localized to proximal tubular cells. TLR-9 levels correlated with proteinuria and tubulointerstitial injury to the extent that a cyclin-dependent kinase inhibitor, while reducing proteinuria and renal structural damage, prevented tubular TLR-9 generation in lupus mice. Consistently, exaggerated TLR-9 staining was found in proximal tubular cells of lupus patients, which correlated with tubulointerstitial damage. DNA-containing immune complexes purified from sera of patients with lupus induced TLR-9 in cultured proximal tubular cells. This was prevented by CCGG-rich short oligonucleotides, specific antagonists of CpG DNA, indicating that the DNA component of immune complexes was required for TLR-9 stimulation.These findings suggest that tubular TLR-9 activation has a pathogenetic role in tubulointerstitial inflammation and damage in experimental and human lupus nephritis, and they indicate a novel target for future therapies." @default.
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• W2149641211 date "2007-01-01" @default.
• W2149641211 modified "2023-10-16" @default.
• W2149641211 title "Involvement of renal tubular toll-like receptor 9 in the development of tubulointerstitial injury in systemic lupus" @default.
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• W2149641211 doi "https://doi.org/10.1002/art.22524" @default.
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