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Inflammasome Activation Mediates Apoptotic and Pyroptotic Death in Astrocytes Under Ischemic Conditions

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An Author Correction to this article was published on 21 September 2023

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Abstract

Inflammation is a hallmark mechanism of ischemic stroke-induced brain injury. Recent studies have shown that an intracellular multimeric protein complex known as an inflammasome is a key factor for inducing an inflammatory response, and apoptotic and pyroptotic cell death in ischemic stroke. Inflammasome assembly leads to the activation of pro-inflammatory caspases, and the maturation and secretion of pro-inflammatory cytokines IL-1β and IL-18. While the role of inflammasomes in ischemic stroke-induced neuronal death, and microglial activation and cell death have been established, little is known about the role of inflammasomes in astrocytes under ischemic conditions. In this study, we investigated the expression and activation of inflammasome components in protoplasmic and fibrous astrocytes under ischemic conditions. We found that both protoplasmic and fibrous astrocytes expressed a differential increase in inflammasome protein components, and that their activation promoted maturation of IL-1β and IL-18, and secretion of IL-1β, as well as initiating apoptotic and pyroptotic cell death. Pharmacological inhibition of caspase-1 decreased expression of cleaved caspase-1 and production of mature IL-1β, and protected against inflammasome-mediated apoptotic and pyroptotic cell death. Overall, this study provides novel insights into the role of inflammasome signaling in astrocytes under ischemic conditions.

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Funding

This work was supported by the National Medical Research Council Research Grants (NMRC-CBRG-0102/2016 and NMRC/OFIRG/0036/2017) in Singapore and the National Health and Medical Research Council of Australia (Grant Identification Number 2019100).

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Author notes

  1. Bernice Woon Li Lee and Yi Jing Sng have contributed equally to the manuscript.

Authors and Affiliations

  1. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Lap Jack Wong, Bernice Woon Li Lee, Yi Jing Sng, Luting Poh, Vismitha Rajeev, Sharmelee Selvaraji & Thiruma V. Arumugam

  2. Memory Aging and Cognition Centre, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Luting Poh, Vismitha Rajeev & Sharmelee Selvaraji

  3. NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore

    Sharmelee Selvaraji

  4. Centre for Cardiovascular Biology and Disease Research and Department of Microbiology, Anatomy, Physiology and Pharmacology, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC, Australia

    Grant R. Drummond, Christopher G. Sobey & Thiruma V. Arumugam

  5. School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea

    Thiruma V. Arumugam

  6. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    David Y. Fann

  7. Healthy Longevity Translational Research Programme (HLTRP), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    David Y. Fann

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  1. Lap Jack Wong
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Contributions

Study conception and design: TVA, and DYF; experiment or data collection: WLJ, BWLL, and YJS: data analysis: WLJ, BWLL, YJS, LP, VR, SS, DYF, and TVA; data interpretation: WLJ, BWLL, and YJS, TVA, and DYF; writing-manuscript preparation: TVA, DYF, GRD, CGS; supervision, and intellectual input and administration: TVA, and DYF. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Thiruma V. Arumugam or David Y. Fann.

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The original online version of this article was revised: Subsequent to the online publication, an error was identified in figure 2G, originating from an oversight during the assembly of figure 2. Immediate corrective actions have been taken to address this error. The original article has been corrected.

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Wong, L.J., Lee, B.W.L., Sng, Y.J. et al. Inflammasome Activation Mediates Apoptotic and Pyroptotic Death in Astrocytes Under Ischemic Conditions. Neuromol Med 25, 533–544 (2023). https://doi.org/10.1007/s12017-023-08753-2

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