Abstract
Psoriasis is a skin disease that is accompanied by oxidative stress resulting in modification of cell components, including proteins. Therefore, we investigated the relationship between the intensity of oxidative stress and the expression and activity of the proteasomal system as well as autophagy, responsible for the degradation of oxidatively modified proteins in the blood cells of patients with psoriasis. Our results showed that the caspase-like, trypsin-like, and chymotrypsin-like activity of the 20S proteasome in lymphocytes, erythrocytes, and granulocytes was lower, while the expression of constitutive proteasome and immunoproteasome subunits in lymphocytes was increased cells of psoriatic patients compared to healthy subjects. Conversely, the expression of constitutive subunits in erythrocytes, and both constitutive and immunoproteasomal subunits in granulocytes were reduced. However, a significant increase in the autophagy flux (assessed using LC3BII/LC3BI ratio) independent of the AKT pathway was observed. The levels of 4-HNE, 4-HNE-protein adducts, and proteins carbonyl groups were significantly higher in the blood cells of psoriatic patients. The decreased activity of the 20S proteasome together with the increased autophagy and the significantly increased level of proteins carbonyl groups and 4-HNE-protein adducts indicate a proteostatic imbalance in the blood cells of patients with psoriasis.
Highlights
Psoriasis is a chronic inflammatory autoimmune disease of the skin and joints
Inflammatory cytokines, such as interleukins IL-23 and IL-6, are produced by dendritic cells and macrophages. These cytokines facilitate the differentiation of Th17 cells, which secrete IL-17 and other mediators that stimulate the hyperproliferation of epidermal cells and contribute to abnormal keratinocyte differentiation [2]
Our findings indicate a significant increase in autophagy units in the blood cells of patients with psoriasis
Summary
Psoriasis is a chronic inflammatory autoimmune disease of the skin and joints. Its pathogenesis is thought to include interactions between genetic factors (for example, the HLACw6 and HLACw7 tissue compatibility complex alleles) and environmental factors such as bacterial or viral infections, injuries, and stress [1]. In addition to the degradation of oxidized proteins, the proteasome is involved in the regulation of many other signaling pathways, including cell differentiation, proliferation, and apoptosis, as well as transcription activation and angiogenesis [27]. Consistent with these findings, the selective proteasome inhibitor PS-519 prevents IκB degradation and inhibits downstream NF-κB signaling, reducing T cell activation in vitro and in vivo It is effective in the treatment of psoriasis in the murine SCID-hu model [31]. The study aimed to link the severity of oxidative stress (assessed by the level of lipid peroxidTahtieornefoarned, tohxeidstautdivyeapimroetedintomlinodkitfhiceatsieovnesr)itwy iothf otxhiedaetxipveresstsrieosns (oafssthesesepdrobtyeatshoemleavl eslyosftelmipid anpdearouxtoidpahtaiognyainndthoexbidloaotidveceplrlos toefinpsmooridaisfiiscaptaiotinesn)tws.ith the expression of the proteasomal system and autophagy in the blood cells of psoriasis patients
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