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Sirolimus inhibits NLRP3. 21 / 21
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"Rapamycin, a potent autophagy inducer, inhibits the activation of NLRP3 inflammasomes and the production of IL-1β and IL-18 by eliminating mitochondrial ROS in macrophages [247], while 3-MA promotes the accumulation of mitochondrial ROS and the subsequent overactivation of the NLRP3 inflammasome [95]."
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"Ko et al. found that autophagy inducer rapamycin restricted a feedback loop of NLRP3 inflammasome-p38 MAPK-NF-kappaB pathways in autophagy- and p62 dependent manners [XREF_BIBR]."
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"Rapamycin inhibits NLRP3 inflammasome activation through autophagy induction."
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"Rapamycin inhibits the activation of NOD-like receptor protein 3 (NLRP3) by regulating the mammalian target of rapamycin (mTOR) to treat obstructive sleep apnea-related renal injury."
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"Sirolimus can also induce the degradation of pro-IL-1β, and prevent maturation and secretion of cytokines by inhibiting NLRP3 inflammasome activity [33]."
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"A recent study reported that NLRP3 signaling and pyroptosis was inhibited by rapamycin (which binds to mammalian target of rapamycin [mTOR]) in macrophages ."
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"Rapamycin effectively downregulated the mRNA expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), toll-like receptor 4 (TLR4), nucleotide binding oligomerization domain-like receptors (NLR) family pyrin domain-containing 3 (NLRP3), and Caspase-1, and suppressed the infiltration of neutrophils and macrophages."
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"Additionally, mTORC1 can activate NLRP3 inflammasome in macrophages, whereas sirolimus sufficiently restricts NLRP3 inflammasome via mTORC1 inhibition [32]."
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"Interestingly, Rapamycin inhibition of the NLRP3 inflammasome seemed to affect Caspase-1 activation as shown in Figure XREF_FIG D. Similar observations were made for MCC950, consistent with prior published observations."
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"Delayed oseltamivir and sirolimus combined treatment could suppress NLRP3 inflammasome mediated secretion of IL-1beta and IL-18, resulting in attenuation of H1N1 induced lung injury [XREF_BIBR]."
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"Like TAS, both INK-128 (inhibiting both mTORC1 and mTORC2) and rapamycin (inhibiting mTORC1 only) also inhibited NLRP3 inflammasome activation, though their effects on mTOR signaling were different."
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"p62 and SQSTM1 is essential for autophagy induction and NLRP3 inflammasome inhibition by rapamycin."
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"In addition, studies have found that the administration of rapamycin at the early stage of the cytokine storm can prevent COVID-19 from progressing to a severe form by downregulating the senescence-associated secretory phenotype, mTOR-NLRP3-IL-1β axis, and IL-6 pathway, as well as decreasing the number of senescent T cells [251], suggesting that rapamycin as a potent autophagy activator may inhibit the NLRP3 inflammasome via autophagy induction."
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"In an experimental animal model of H1N1 influenza, rapamycin in combination with oseltamivir reduced viral replication and the NLRP3 inflammasome."
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"In conclusion, our results suggest that sirolimus suppresses NLRP3 inflammasome, which is correlated with inhibited NF-κB activation and ROS production, and induced autophagy after pH1N1 infection; however, it is not clear whether other inflammasomes, such as AIM2, are also inhibited.Our experimental and clinical studies have revealed that dysregulated cytokine storm and excessive inflammatory cell infiltration are associated with disease severity [2–6]."
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"JSH23 and rapamycin both attenuated NLRP3 activation, while cells treated with LEU showed high levels of NLRP3, ASC, and Casp1 p20."
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"Researches demonstrate that rapamycin reduces NLRP3 inflammasome activation by inhibiting the mTOR and NF-kappaB pathway in macrophages, and mTOR regulates NLRP3 inflammasome activation via reactive oxygen species in murine lupus."
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"We first examined whether rapamycin inhibits NLRP3 inflammasome activation in macrophages."
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"Results : We found that rapamycin reduced NLRP3 inflammasome activation in macrophages."
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"Indeed, inhibition of mitophagy by 3-methyladenine resulted in Mphi polarization towards M1 phenotype, while rapamycin mediated induction of autophagy suppressed the mtROS and NLRP3 inflammasome activation and favored Mphi polarization towards M2 phenotype."
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"Local intra-articular injection of rapamycin inhibits NLRP3 activity and prevents osteoarthritis in mouse DMM models."
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