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Hydroxychloroquine inhibits TLR7. 27 / 29
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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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"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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"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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"Notably, hydroxychloroquine, recommended for most individuals with lupus, can gently reduce TLR7 activation by inhibiting endosome acidification."
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"Existing treatments already target this pathway ; notably , hydroxychloroquine and bafilomycin inhibit endosome acidification and / or maturation , thereby inhibiting both TLR7 and TLR9 signalling94 ."
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"Hydroxychloroquine inhibits proteolytic processing of endogenous TLR7 protein in human primary plasmacytoid dendritic cells.The Toll-like receptor 7 (TLR7) is essential for the induction of antiviral immunity but is also involved in the pathogenesis of systemic lupus erythematosus (SLE), an autoimmune disease with a strong female bias [1, 2] ."
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"For instance, hydroxychloroquine, whose effect in cells is to increase the pH in acidic organelles, has been shown to prevent endosomal cleavage of TLR7, which in turn inhibits its function [188]."
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"This was also seen after removal of patients prescribed the glucocorticoid prednisone, which has been reported to inhibit NF-kappaB activation, and hydroxychloroquine (Plaquenil (R)) inhibiting TLR7 and -9 signaling."
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"We also measured the halflife of TLR7 and the impact of HCQ on pDC activation in response to synthetic TLR ligands, as well as viruses, including SARS-CoV2.Inhibition of endosomal acidification in fresh PBMCs inhibits TLR7 cleavage and results in accumulation of full-length protein."
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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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"As HCQ downregulates TLR7-dependent proximal signaling, we analyzed the impact of HCQ treatment on the capacity of IL-3-pDCs to produce IFN-a, IP-10 and TNFa in response to activation with TLR7 ligands, including viruses."
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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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"Our finding suggests that the major pathway by which HCQ inhibits TLR7-signaling may rely on its capacity to inhibit endosomal pH acidification thereby blunting the functional maturation of TLR7 protein."
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"This protective effect is attributed to hydroxychloroquine’s ability to inhibit Toll-like receptor 7 stimulation, preventing a cascade of events that lead to the secretion of pro-inflammatory substances and subsequent cardiac fibrosis (13, 14)."
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"HCQ and Bafilomycin A1 inhibit the cleavage of endogenous TLR7 in human pDCs."
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"HCQ inhibits TLR7-dependent recognition of SARS-CoV2 by pDCs."
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"HCQ treatment only significantly inhibited TLR7 responses."
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"At the same time , hydroxychloroquine and azithromycin inhibit TLR7 / 8 signaling [ 92 ] , [ 93 ] Selective interference of PD-1 / PDL-1 pathway with antagonistic antibodies against PD-1 receptor reduces type I IFN response and ISG expression in chronic HIV infection [ 31 ] , [ 32 ] , [ 33 ] ."
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"In our study, TLR7 antagonist HCQ appeared to reduce disease severity slightly in tEAU mice (data not shown)."
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"However, retinal toxicity and macular retinopathy are well-known side effects of the TLR7 antagonist HCQ (67), a derivative of chloroquine."
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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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"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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"Hydroxychloroquine inhibits disruption of annexin A5 by Anti beta 2 glycoprotein 1 antibodies and reduces TLR-7 activation in vitro, reducing thrombosis in APS mouse models [171,178]."
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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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"Whether HCQ can prevent endogenous TLR7 cleavage in primary immune cells, such as plasmacytoid dendritic cells (pDCs), had never been examined."
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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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"HCQ inhibition of TLR-7 is considered particularly significant for ameliorating SLE disease and anti-RO/SSA antibody-mediated congenital heart block [69], whereas hypersensitivity to TLR-9 was acknowledged in TNF receptor-associated periodic syndrome."
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