Abstract
Despite the constantly updated knowledge regarding the alterations occurring in the cells of patients with psoriasis, the status and the role of the lysosome, a control center of cell metabolism, remain to be elucidated. The architecture of the epidermis is largely regulated by the action of lysosomes, possibly activating signaling pathways in the cellular crosstalk of keratinocytes—epidermal cells—with infiltrating immune cells. Thus, in the present study, lysosome alterations were examined in vitro and in situ using a two-dimensional (2D) keratinocyte model of HaCaT cells with “psoriasis-like” inflammation and skin specimens, respectively. Specific fluorescence and immunohistochemical staining showed an augmented level of acidic organelles in response to keratinocyte activation (mimicking a psoriatic condition while maintaining the membrane integrity of these structures) as compared with the control, similar to that seen in skin samples taken from patients. Interestingly, patients with the most pronounced PASI (Psoriasis Area and Severity Index), BSA (Body Surface Area), and DLQI (Dermatology Life Quality Index) scores suffered a high incidence of positive lysosomal-associated membrane protein 1 (LAMP1) expression. Moreover, it was found that the gene deregulation pattern was comparable in lesioned (PP) and non-lesioned (PN) patient-derived skin tissue, which may indicate that these alterations occur prior to the onset of the characteristic phenotype of the disease. Changes in the activity of genes encoding the microphthalmia family (MiT family) of transcription factors and mammalian target of rapamycin complex 1 (MTORC1) were also observed in the in vitro psoriasis model, indicating that the biogenesis pathway of this arm is inhibited. Interestingly, in contrast to the keratinocytes of HaCaT with “psoriasis-like” inflammation, LAMP1 was up-regulated in both PP and PN skin, which can be a potential sign of an alternative mechanism of lysosome formation. Defining the molecular profile of psoriasis in the context of “the awesome lysosome” is not only interesting, but also desired; therefore, it is believed that this paper will serve to encourage other researchers to conduct further studies on this subject.
Highlights
In recent years, increasing attention has been paid to the contribution of lysosomes to autoimmune diseases [1,2]
To carry out studies assessing the potential contribution of lysosomes to the disturbed processes of apoptosis and autophagy, abnormalities of sphingolipid and ceramide metabolism pathways, incorrect presentation of antigens by major histocompatibility complex (MHC) class I and II molecules or increased transcription of genes encoding selected proinflammatory cytokines and chemokines—processes being deregulated in this dermatosis, the gaps in knowledge must be filled using recently developed “lysosomics”, therein in relevance to psoriasis
Since the presence of lysosomal-associated membrane protein 1 (LAMP1) is noticeable in the same cells in culture, as evidenced by immunofluorescence, the effect on LAMP1 mRNA expression observed in the present study suggests post-transcriptional control of LAMP1 production in HaCaT cells
Summary
In recent years, increasing attention has been paid to the contribution of lysosomes to autoimmune diseases [1,2]. The relatively recent, intensively developing field of “lysosomics” provides a range of important information regarding the role of lysosomes in the inflammatory response and autoimmune conditions [4,5,6,7], despite the fact that the first signs of lysosomal involvement in inflammatory diseases were identified decades ago [8]. These investigations were only superficially concerned with inflammatory skin diseases, including the most common human skin autoimmune disease, psoriasis (PsO) [9,10,11,12]. In addition to the human immortalized keratinocyte HaCaT model, skin tissue from biopsies of controls, healthy individuals, and patients with psoriasis, from the involved and noninvolved psoriatic skin, were evaluated
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