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• W2904255034 abstract "Mycobacterium tuberculosis ( Mtb ) is the pathogen responsible for tuberculosis, a leading cause of illness and death worldwide. Growing evidence suggests that the proinflammatory cytokine IL ‐32 plays a major role in host defences against pathogens such as Mtb . IL ‐32 exists in six alternatively spliced isoforms, but antituberculosis effects have been reported only for some of them. In this study, we examined the effect of all six IL ‐32 isoforms on Mtb replication in the murine macrophage cell line RAW 264.7. Compared with cells transfected with the other isoforms, IL ‐32ε‐transfected cells exhibited the strongest antituberculosis effect and the highest rate of Mtb‐ induced apoptosis. Of note, this apoptosis pathway was independent of caspase‐3 activation. Instead, N‐Myc interactor ( NMI ), an inhibitor of Wnt signalling, was a key player in IL ‐32ε‐mediated apoptosis by inhibiting Wnt/β‐catenin signalling and thereby activating c‐Myc‐mediated apoptosis. Moreover, we identified two cis ‐acting elements that are binding sites for the transcriptional regulators paired box 6 ( PAX 6) and transcription factor CP 2 ( TFCP 2) in the promoter of NMI and these elements proved essential for IL ‐32ε‐induced upregulation of Nmi expression. Furthermore, IL ‐32ε‐mediated activation of the mitogen‐activated protein kinase p38 also contributed to NMI upregulation. In conclusion, our results demonstrate that Mtb infection‐induced IL ‐32ε‐mediated apoptosis in macrophages plays a key role in host defences against Mtb ." @default.
• W2904255034 created "2018-12-22" @default.
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• W2904255034 date "2018-12-26" @default.
• W2904255034 modified "2023-10-08" @default.
• W2904255034 title "Interleukin‐32ε induces caspase‐independent apoptosis mediated by N‐Myc interactor in macrophages infected with <i>Mycobacterium tuberculosis</i>" @default.
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• W2904255034 doi "https://doi.org/10.1111/febs.14717" @default.
• W2904255034 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30521142" @default.
• W2904255034 hasPublicationYear "2018" @default.
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