Journal Article

FZJ-2022-00500

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Erythropoietin Abrogates Post-Ischemic Activation of the NLRP3, NLRC4, and AIM2 Inflammasomes in Microglia/Macrophages in a TAK1-Dependent Manner

Heinisch, O. (Corresponding author) ; Zeyen, T. ; Goldmann, T. ; Prinz, M. ; Huber, M. ; Jung, J. ; Arik, E. ; Habib, S. ; Slowik, A. ; Reich, A. ; Schulz, J. B.FZJ* ; Habib, P. (Corresponding author)

2022
Springer New York, NY

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Please use a persistent id in citations: http://hdl.handle.net/2128/31253  doi:10.1007/s12975-021-00948-8

Abstract: Inflammasomes are known to contribute to brain damage after acute ischemic stroke (AIS). TAK1 is predominantly expressed in microglial cells and can regulate the NLRP3 inflammasome, but its impact on other inflammasomes including NLRC4 and AIM2 after AIS remains elusive. EPO has been shown to reduce NLRP3 protein levels in different disease models. Whether EPO-mediated neuroprotection after AIS is conveyed via an EPO/TAK1/inflammasome axis in microglia remains to be clarified. Subjecting mice deficient for TAK1 in microglia/macrophages (Mi/MΦ) to AIS revealed a significant reduction in infarct sizes and neurological impairments compared to the corresponding controls. Post-ischemic increased activation of TAK1, NLRP3, NLRC4, and AIM2 inflammasomes including their associated downstream cascades were markedly reduced upon deletion of Mi/MΦ TAK1. EPO administration improved clinical outcomes and dampened stroke-induced activation of TAK1 and inflammasome cascades, which was not evident after the deletion of Mi/MΦ TAK1. Pharmacological inhibition of NLRP3 in microglial BV-2 cells did not influence post-OGD IL-1β levels, but increased NLRC4 and AIM2 protein levels, suggesting compensatory activities among inflammasomes. Overall, we provide evidence that Mi/MΦ TAK1 regulates the expression and activation of the NLRP3, NLRC4, AIM2 inflammasomes. Furthermore, EPO mitigated stroke-induced activation of TAK1 and inflammasomes, indicating that EPO conveyed neuroprotection might be mediated via an EPO/TAK1/inflammasome axis.

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Contributing Institute(s):

1. Jara-Institut Quantum Information (INM-11)

Research Program(s):

1. 5252 - Brain Dysfunction and Plasticity (POF4-525) (POF4-525)

Appears in the scientific report 2022

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Springer ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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