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Inhibition of the PERK/TXNIP/NLRP3 Axis by Baicalin Reduces NLRP3 Inflammasome‐Mediated Pyroptosis in Macrophages Infected with <i>Mycobacterium tuberculosis</i>

Yan Fu, Jingjing Shen, Yinhong Li, Fanglin Liu, Bangzuo Ning, Yuejuan Zheng, Xin Jiang

2021Mediators of Inflammation44 citationsDOIOpen Access PDF

Abstract

Mycobacterium tuberculosis (Mtb) remains a significant threat to global health as it induces granuloma and systemic inflammatory responses during active tuberculosis. Mtb can induce macrophage pyroptosis, leading to the release of IL‐1 β and tissue damage, promoting its spread. Here, we established an in vitro Mtb‐infected macrophage model to seek an effective antipyroptosis agent. Baicalin, isolated from Radix Scutellariae, was found to reduce pyroptosis in Mtb‐infected macrophages. Baicalin could inhibit activation of the PERK/eIF2 α pathway and thus downregulates TXNIP expression and subsequently reduces activation of the NLRP3 inflammasome, resulting in reduced pyroptosis in Mtb‐infected macrophages. In conclusion, baicalin reduced pyroptosis by inhibiting the PERK/TXNIP/NLRP3 axis and might thus be a new adjuvant host‐directed therapy (HDT) drug.

Topics & Concepts

PyroptosisInflammasomeTXNIPBaicalinMacrophageMycobacterium tuberculosisTuberculosisMicrobiologyCaspase 1MedicineInflammationImmunologyChemistryIn vitroBiologyBiochemistryPathologyThioredoxinHigh-performance liquid chromatographyChromatographyOxidative stressEndocrinologyInflammasome and immune disordersinterferon and immune responsesHeme Oxygenase-1 and Carbon Monoxide