| First Author | Trstenjak-Prebanda M | Year | 2023 |
| Journal | Cells | Volume | 12 |
| Issue | 23 | PubMed ID | 38067160 |
| Mgi Jnum | J:363991 | Mgi Id | MGI:7574986 |
| Doi | 10.3390/cells12232731 | Citation | Trstenjak-Prebanda M, et al. (2023) Stefin B Inhibits NLRP3 Inflammasome Activation via AMPK/mTOR Signalling. Cells 12(23) |
| abstractText | 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-beta (IL-1beta) due to increased inflammasome activation in bone marrow-derived macrophages. Here, we report lower interleukin 1-beta 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. |
