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Hydroxychloroquine inhibits TLR9. 37 / 40
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"Other Toll-like targets are of interest as well, such as TLR-7 and TLR-9 blockage by hydroxychloroquine, which has been used successfully in inflammatory disorders such as systemic lupus erythematosus [52] and post-Lyme’s arthritis [53]."
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"Since hydroxychloroquine and chloroquine are inhibitors of the anti-viral PRRs TLR9 and cGAS, they may provide a means of improving AAV transduction by modulating anti-viral responses during gene therapy."
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"Hydroxychloroquine is a potent inhibitor of TLR-9, and to a lesser extent TLR-7 and TLR-8, and inhibits antigen processing and presentation via alkalinization of proteasomes [XREF_BIBR, XREF_BIBR]."
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"In antigen-presenting cells, HCQ also reduced constitutive activation of the endo-lysosomal protease legumain and toll-like receptor 9, thereby reducing cytokine production, but it had little apparent impact on constitutive antigen processing and peptide presentation."
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"In vitro and animal APS models showed that HCQ can reverse aPL mediated platelet activation, the binding of aPL-β2GPI complexes to phospholipid bilayers, and the activation of TLR3, TLR7, and TLR9 rec[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"For example, hsa-miR-30a has been shown to sensitize LIHC cells to a combined therapy of hydroxychloroquine and sorafenib by repressing TLR9 [79]."
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"The TLR7 to TLR9 blocker hydroxychloroquine has been in use in patients with lupus for more than 50years, but oligonucleotide based inhibitors of TLR7 to TLR9, despite showing promise in animal models of lupus, have not reached the primary end point in a recent phase 1 trial."
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"However, HCQ reversed the effect of TLR9 agonist on third-trimester placenta explants secretion, leading to a reduction in sFlt-1 production and improvement of sFlt1/PlGF ratio (Scott et al., 2019)."
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"HCQ was much less potent than E6742 in inhibiting TLR7/8 agonist-induced IL-6 and IFN-α production, though HCQ potently inhibited TLR9 activation."
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"Another mechanism of action of hydroxychloroquine can block TLR7 and TLR9, the signaling of which leads to the production of interferon-α and its effector cytokines."
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"The mechanism of the inhibition of endosomal TLR 7 and TLR9 by HCQ and CQ has been presented in Fig. 5 [ 58 ] ."
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"Taken together, hydroxychloroquine markedly suppresses the TLR9 mediated human B cell functions during inflammatory processes."
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"HCQ also is an antagonist of TLR9 (and the RNA sensor, TLR7) ( Scott et al., 2019 ), and may also inhibit cGAS ( Chandler et al., 2020 )."
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"Additionally, although we demonstrated a role for cffDNA as a DAMP in its ability to reduce trophoblast migration, more mechanistic studies are needed to definitively demonstrate the specific DNA sens[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Since hydroxychloroquine, which can inhibit TLR9, reverses cffDNA inhibition of trophoblast migration, it is intriguing to consider exploring the use of this medication in women at high risk for preec[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"A previous study established that HCQ significantly inhibited TLR9-mediated human B cell function during inflammation [24] ."
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"The mechanism of the inhibition of endosomal TLR 7 and TLR9 by HCQ and CQ has been presented in Fig."
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"HCQ blocking TLR9 protects against hepatic I/R injury by inhibiting NETs formation, which may suggest utility of HCQ or other TLR9 agonists for preventing hepatic I/R injury in clinical practices."
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"Indeed, in vivo treatment with HCQ in SLE patients has been shown to inhibit TLR7 and TLR9-dependent activation of pDCs upon ex vivo exposure of pDCs with specific TLR ligands [24] ."
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"Mechanistically , HCQ down-regulated the expression of TLR9 not only in healthy donor PBMC-derived DCs stimulated by RA patient serum , but also in LN DCs of CIA mice and CpG-activated BMDCs ."
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"Hydroxychloroquine works by inhibiting the binding of TLR9 to the ligand CPG-DNA so that TLR9 cannot be activated (Rutz et al., 2004)."
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"In rheumatoid arthritis and systemic lupus erythematosus, hydroxychloroquine has been suggested to mediate its anti-inflammatory action by inhibiting the activation of TLR7 and TLR9 that reside in endosomal/lysosomal compartments 23."
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"On the contrary, Yu et al., have hypothesized that hydroxychloroquine and other antimalarials, by inhibiting the toll like receptor-9 (TLR9), may induce persistence of HPV in lupus erythematosus patients."
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"In addition , hydroxychloroquine ( HCQ ) and ODN2088 were used to inhibit TLR9 to investigate the role of TLR9 on caspase3 / GSDME-mediated pyroptosis ."
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"Nonetheless, given the proposed mechanism of action via TLR9, it seems possible that hydroxychloroquine and chloroquine might prevent the activation of nucleic acid sensors cGAS and TLR9 through a common mechanism such as alteration of the structural configuration of the DNA substrate [33,34]."
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"Again, HCQ prevented the up-regulation of TLR9 as anticipated (XREF_FIG B)."
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"Given that the endosomal maturation inhibitor hydroxychloroquine inhibits TLR9 activation and is a common treatment for SjS XREF_BIBR, we injected NOD and BALB/c mice with ODN2088, which dramatically increased salivation in NOD mice (p = 0.0018) (XREF_FIG)."
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"Hydroxychloroquine blocks TLR9 activation by mitochondrial DNA in vitro and may attenuate flares of rhabdomyolysis in 6 patients treated."
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"Hydroxychloroquine powerfully inhibits TLR9 through impaired endosomal acidification [41]."
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"HCQ has been reported to abrogate endosomal TLR (TLR3, TLR7, TLR8, and TLR9) responses by preventing acidification [64] ."
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"Hydroxychloroquine inhibits TLR9 and to a lesser extent TLR7 and TLR8 signaling."
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"In fact, hydroxychloroquine, a mainstay treatment for SLE patients, is known to suppress TLR7 and TLR9 signaling upstream of MyD88 through intercalation into nucleotides (Kuznik et al., 2011)."
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"We supposed that the reasons are as follows : ( 1 ) the immune regulation function of HCQ in suppressing the secretion of pro-inflammatory factors [ 11,12 ] , which can be explained by our results that HCQ diminished the levels of pro-inflammatory factors including IFN-alpha , TNF-alpha , IL-1beta and IL-12 by blocking TLR9 ; ( 2 ) however , as mentioned above , HCQ could only blocking TLR9 , so it just partially reduces the production of inflammatory cytokines ."
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"Again , HCQ prevented the up-regulation of TLR9 as anticipated ( Fig. 4B ) ."
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"The injection of hydroxychloroquine (HCQ) that interferes with endosomal function and inhibits TLR9 responses also abrogated central B cell tolerance in humanized mice (Fig. S1, E–J; Kuraoka et al., 2017)."
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"These responses were suppressed by hydroxychloroquine (HCQ) [11], which inhibits endosomal acidification and subsequent cleavage induced activation of TLR9 [85]."
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"A role of TLRs in HIV induced immune activation is also supported by the reduction in immune activation by TLR7 and TLR9 signaling inhibitors such as chloroquine and hydroxychloroquine [XREF_BIBR, XREF_BIBR]."
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