IndraLab

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Lactate inhibits NLRP3. 10 / 10
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"In the chronic inflammatory response, lactate accumulates in large amounts, and the lactate/GPR81 pathway inhibits either the AMPK/NF-κB or ARRB2/NLRP3 signalling pathway to promote resolution of the inflammatory response."
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"Interestingly, lactate negatively regulates TLR induction of the NLRP3 inflammasome and reduces IL-1β production in patients with acute liver injury.35,36 However, NF-кB acts as a double-edged sword in liver disease because its inhibition may not only exert beneficial effects but also negatively impact hepatocyte viability, especially when the inhibition is pronounced.In early cirrhosis, NF-кB plays a protective role against hepatocyte death."
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"Inhibition of pyruvate oxidation reprogrammed pyruvate metabolism from mitochondrial pyruvate driven respiration to cytoplasmic lactic acid fermentation and further activates the regulator of NLRP3 inflammasome activation, lactate dependent PKR phosphorylation."
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"Further, lactate suppresses the induction of the NLRP3 inflammasome and IL1beta via GPR81 activation, regulates TLR activation via interactions with arrestin B2 downstream of GPR81, and protects against inflammatory injury in pancreatitis and hepatitis models through GPR81 signaling."
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"After gavage of apigenin, apigenin can significantly reduce the level of lactate dehydrogenase (LDH) in liver tissue ignited by HFD and reduce the levels of NLRP3 (NOD-like receptor family pyrin domain containing 3), the N-terminal domain of GSDMD (GSDMD-N), cleaved-caspase 1, cathepsin B (CTSB), interleukin-1β (IL-1β) and interleukin-18 (IL-18) protein expression and the colocalization of NLRP3 and CTSB and increase the level of lysosomal associated membrane protein-1 (LAMP-1) protein expression, thus alleviating cell pyroptosis."
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"The inhibition of the NLRP3 inflammasome complex by lactate [ xref ] may also play a role in the antidepressant-like effect of lactate since this inflammasome has been widely recognized as being crucial for the development of depressive symptoms under inflammatory conditions [ xref ]."
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"In macrophages and monocytes, increasing concentrations of lactate reduced TLR4 mediated induction of Il1B, Nlrp3, and Casp1; activation of NFkappaB; release of IL1beta; and cleavage of CASP1."
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"Lactate reduces inflammasomes’ activation, especially that of nod-like receptor protein 3 (NLRP3), and consequently, the production of pro-inflammatory cytokines is also reduced via GPR81 signaling (Hu et al., 2020)."
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"The inhibition of the NLRP3 inflammasome complex by lactate can be mediated by the activation of HCAR1 (GPR81) via a mechanism involving the intracellular adaptor protein β-Arrestin 2, and by attenuating NF-kB activity, thus reducing inflammation [ xref , xref ]."
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"Inhibition of lactate dehydrogenase with GSK2837808A reduced lactate production and activity of the NLRP3 inflammasome regulator, phosphorylated protein kinase R (PKR), but did not reduce the common trigger of NLRP3 inflammasome, potassium efflux, or reactive oxygen species (ROS) production."
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