Skin aging is an extremely important medical and social problem in the modern world. Therefore, a goal of the present work was to estimate changes in the numbers of fibroblast-like cells, proliferating cells nuclear antigen-positive cells, CD45-positive cells, mast cells, and eosinophils in human dermis at different ages. Skin specimens from human fetuses that died antenatally from 20 to 40 weeks of pregnancy and humans who died from different causes from 1 day to 85 years of life were used for the study. Results showed a decrease in a total number and the number of proliferating cells nuclear antigen-positive fibroblast-like cells in dermis with progression of age. The numbers of CD45-positive cells and mast cells are gradually increased with aging. Eosinophils are almost absent in dermis independently on age. Mast cells are probably a main factor that potentially can be involved in tissue damage and aging changes in skin. Mast cells should be regarded as an important target for anti-aging therapy.
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.
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