Stefin B Inhibits NLRP3 Inflammasome Activation via AMPK/mTOR Signalling - Inserm - Institut national de la santé et de la recherche médicale
Article Dans Une Revue Cells Année : 2023

Stefin B Inhibits NLRP3 Inflammasome Activation via AMPK/mTOR Signalling

Résumé

Stefin B (cystatin B) is an inhibitor of lysosomal and nuclear cysteine cathepsins. The gene for stefin B is located on human chromosome 21 and its expression is upregulated in the brains of individuals with Down syndrome. Biallelic loss-of-function mutations in the stefin B gene lead to Unverricht–Lundborg disease-progressive myoclonus epilepsy type 1 (EPM1) in humans. In our past study, we demonstrated that mice lacking stefin B were significantly more sensitive to sepsis induced by lipopolysaccharide (LPS) and secreted higher levels of interleukin 1-β (IL-1β) due to increased inflammasome activation in bone marrow-derived macrophages. Here, we report lower interleukin 1-β processing and caspase-11 expression in bone marrow-derived macrophages prepared from mice that have an additional copy of the stefin B gene. Increased expression of stefin B downregulated mitochondrial reactive oxygen species (ROS) generation and lowered the NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in macrophages. We determined higher AMP-activated kinase phosphorylation and downregulation of mTOR activity in stefin B trisomic macrophages—macrophages with increased stefin B expression. Our study showed that increased stefin B expression downregulated mitochondrial ROS generation and increased autophagy. The present work contributes to a better understanding of the role of stefin B in regulation of autophagy and inflammasome activation in macrophages and could help to develop new treatments.
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hal-04747434 , version 1 (29-10-2024)

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Mojca Trstenjak-Prebanda, Monika Biasizzo, Klemen Dolinar, Sergej Pirkmajer, Boris Turk, et al.. Stefin B Inhibits NLRP3 Inflammasome Activation via AMPK/mTOR Signalling. Cells, 2023, 12 (23), pp.2731. ⟨10.3390/cells12232731⟩. ⟨hal-04747434⟩
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