A role for stefin B (cystatin B) in inflammation and endotoxemia.

Stefin B (cystatin B) is an endogenous cysteine cathepsin inhibitor, and the loss-of-function mutations in the stefin B gene were reported in patients with Unverricht-Lundborg disease (EPM1). In this study we demonstrated that stefin B-deficient (StB KO) mice were significantly more sensitive to the lethal LPS-induced sepsis and secreted higher amounts of pro-inflammatory cytokines IL-1β and IL-18 in the serum. We further showed that increased caspase-11 gene expression and better pro-inflammatory caspase-1 and -11 activation determined in StB KO bone marrow-derived macrophages resulted in enhanced IL-1β processing. Pretreatment of macrophages with the cathepsin inhibitor E-64d did not affect secretion of IL-1β, suggesting that the increased cathepsin activity determined in StB KO bone marrow-derived macrophages is not essential for inflammasome activation. Upon LPS stimulation, stefin B was targeted into the mitochondria, and the lack of stefin B resulted in the increased destabilization of mitochondrial membrane potential and mitochondrial superoxide generation. Collectively, our study demonstrates that the LPS-induced sepsis in StB KO mice is dependent on caspase-11 and mitochondrial reactive oxygen species but is not associated with the lysosomal destabilization and increased cathepsin activity in the cytosol.

Maher K ，Jerič Kokelj B ，Butinar M ，Mikhaylov G ，Manček-Keber M ，Stoka V ，Vasiljeva O ，Turk B ，Grigoryev SA ，Kopitar-Jerala N ... -  《-》

The Role of Stefin B in Neuro-inflammation.

Kopitar-Jerala N 《Frontiers in Cellular Neuroscience》

Cystatin C Deficiency Increases LPS-Induced Sepsis and NLRP3 Inflammasome Activation in Mice.

Biasizzo M ，Trstenjak-Prebanda M ，Dolinar K ，Pirkmajer S ，Završnik J ，Turk B ，Kopitar-Jerala N ... -  《Cells》

Upregulation of Mitochondrial Redox Sensitive Proteins in LPS-Treated Stefin B-Deficient Macrophages.

Trstenjak Prebanda M ，Završnik J ，Turk B ，Kopitar Jerala N ... -  《Cells》

Stefin B Inhibits NLRP3 Inflammasome Activation via AMPK/mTOR Signalling.

Trstenjak-Prebanda M ，Biasizzo M ，Dolinar K ，Pirkmajer S ，Turk B ，Brault V ，Herault Y ，Kopitar-Jerala N ... -  《Cells》