Epidermis Of Psoriatic Patients Research Articles

Group IVE cytosolic phospholipase A2 limits psoriatic inflammation by mobilizing the anti-inflammatory lipid N-acylethanolamine.

Psoriasis is an inflammatory disorder characterized by keratinocyte hyper-proliferation and Th17-type immune responses. However, the roles of bioactive lipids and the regulation of their biosynthesis in this chronic skin disease are not fully understood. Herein, we show that group IVE cytosolic phospholipase A2 (cPLA2 ε/PLA2G4E) plays a counterregulatory role against psoriatic inflammation by producing the anti-inflammatory lipid N-acylethanolamine (NAE). Lipidomics analysis of mouse skin revealed that NAE species and their precursors (N-acyl-phosphatidylethanolamine and glycerophospho-N-acylethanolamine) were robustly increased in parallel with the ongoing process of imiquimod (IMQ)-induced psoriasis, accompanied by a marked upregulation of cPLA2 ε in epidermal keratinocytes. Genetic deletion of cPLA2 ε exacerbated IMQ-induced ear swelling and psoriatic marker expression, with a dramatic reduction of NAE-related lipids in IMQ-treated, and even normal, skin. Stimulation of cultured human keratinocytes with psoriatic cytokines concomitantly increased PLA2G4E expression and NAE production, and supplementation with NAEs significantly attenuated the cytokine-induced upregulation of the psoriatic marker S100A9. Increased expression of cPLA2 ε was also evident in the epidermis of psoriatic patients. These findings reveal for the first time the in vivo role of cPLA2 ε, which is highly induced in the keratinocytes of the psoriatic skin, promotes the biosynthesis of NAE-related lipids, and contributes to limiting psoriatic inflammation.

Insight into the Metabolite Pattern of Psoriasis: Correlation among Homocysteine, Methionine, and Polyamines

Psoriasis is an incurable dermatological disorder, characterized by increased epidermal cell proliferation. Numerous studies have focused on the modulation of polyamine (PA) metabolism in psoriatic lesions, as well as the relationship between serum homocysteine (Hcy) levels and psoriasis severity. The correlation between Hcy and PA levels has not been investigated, although both of them depend on methionine (Met) loading. The aim of this study was to examine Met, Hcy, and polyamine levels in serum, saliva, lesions, and non-affected skin to investigate the eventual relationship between their levels in skin samples and to assess the correlation of each metabolite among the tested samples. This study was conducted on 24 patients with plaque-form psoriasis vulgaris. The original LC-MS/MS method was used for quantification of analytes. Hyperhomocysteinemia was observed and the serum levels of spermidine (Spd) and spermine (Spm) were also found to be elevated. A significant increase in Met (p < 0.05) and Spm (p < 0.001) concentrations in the psoriatic plaques were found, when compared to the non-affected skin. Significant correlations were established between all polyamines levels and between methionine and spermine in both types of cutaneous samples. This study illustrates the tight relationship between Met and Polyamine levels in epidermis of psoriatic patients. Our results could be helpful in psoriasis treatment, highlighting the importance of the balanced protein diet and intake of vitamins B12 and B9.

Dynamics of expression rates of growth factor proteins in psoriatic patients receiving a phototherapy

Goal. To study the dynamics of expression rates of growth factor proteins in psoriatic patients receiving the PUVA therapy. Materials and methods. The authors conducted a study of 30 patients with psoriasis vulgaris treated with the PUVA therapy. The psoriasis severity and extent of itching were assessed prior to and after the treatment by the PASI index and visual analogue scale, respectively. The expression of semaphorin 3A, amphiregulin, nerve growth factor and PGP 9.5 protein (a nerve fiber marker) in the skin was assessed by the indirect immunofluorescence method. The expression of PGP 9.5 protein was used to assess the quantity and mean length as well as average and total fluorescence intensity of nerve fibers. Results. An increased expression of amphiregulin and nerve growth factor as well as increase in the quantity, mean length and average and total fluorescence intensity of nerve fibers were revealed in the epidermis of psoriatic patients. Following a course of the PUVA therapy, a decrease in the PASI index and extent of itching, reduced expression of amphiregulin and nerve growth factor as well as reduced quantity, mean length and average and total fluorescence intensity of nerve fibers in the epidermis were observed. Direct correlation dependence between the extent of itching, amphiregulin and nerve growth factor expression level and quantity and length of nerve fibers in the epidermis was discovered. Direct correlation dependence between the amphiregulin and nerve growth factor expression level, and average length of nerve fibers in the epidermis was discovered. Conclusion. The itching intensity in psoriatic patients receiving the PUVA therapy is reduced due to the decreased skin expression of the nerve growth factor and amphiregulin.

Impact of inflammation on iron stores in involved and non-involved psoriatic skin

Accumulating evidence supports a role for cellular Fe in cell proliferation, inflammation, and disease tolerance. Psoriasis is a severe inflammatory and hyper proliferative condition of human skin whose aetiology remains poorly understood. Herein, we performed nuclear microscopy techniques to quantify with cellular resolution and high sensitivity the concentration of Fe in lesional (psoriatic plaques) and non-lesional adjacent skin of psoriatic patients. Fe contents were measured across skin depth and along epidermal strata either by quantitatively imaging Fe distribution in regions of interest, or by determining Fe profiles through analysis of sequential points along selected transepts. Both procedures require deconvolution of spectra to project quantitative elemental data through the application of different software codes. Using these approaches a detailed quantitative distribution of Fe was resolved. We show that in both lesional and non-lesional skin, the epidermal profiles of Fe contents showed a peak at the basal layer and that Fe concentration along the basal layer was not uniformly distributed. Typically, Fe levels were significantly higher in epidermal ridges relative to regions above dermal papillae. Lesional skin displayed excess Fe over extended regions above basal layer.In conclusion, we found significantly increased Fe deposits in the epidermis of psoriatic patients, particularly in areas of epidermal hyper proliferation. These findings suggest an important role for Fe in the pathogenesis of psoriasis. They also raise the possibility that manipulation of Fe levels in the skin may become relevant for the clinical management of psoriasis.

Calmodulin‐like skin protein level increases in the differentiated epidermal layers in atopic dermatitis

In atopic dermatitis (AD), the skin barrier is disturbed, and the expression of calcium-dependent S100 proteins and the calcium gradient is also altered in the epidermis. The calmodulin-like skin protein (CLSP), which is expressed in the differentiated epidermis, is believed to modulate the function of calcium-dependent proteins involved in barrier formation and is significantly increased in the epidermis of psoriatic patients. We, therefore, investigated the CLSP level in skin biopsies taken from patients with acute exacerbated and non-exacerbated AD as well as from healthy control subjects. Immunohistochemical, Western blot and ELISA analyses showed significant increases (P < 0.03) in CLSP level in the epidermis from patients with acute exacerbated AD as compared to that from patients with non-exacerbated AD and from control subjects. Such increased expression of CLSP may help re-establish a functional epidermal barrier in acute AD.

Evaluation of epidermal nerve density and opioid receptor levels in psoriatic itch

Psoriasis is a complex, multifactorial inflammatory skin disease with genetic and environmental interactions. Patients with psoriasis exhibit erythematous plaques with itch, but the mechanisms of psoriatic itch are poorly understood. This study was performed to investigate epidermal nerve density and opioid receptor levels in psoriatic skin with or without itch. Twenty-four patients with psoriasis aged between 39 and 82 years were included in this study. The number of epidermal nerve fibres, the levels of semaphorin 3A (Sema3A) and the expression patterns of μ- and κ-opioid systems were examined immunohistologically in skin biopsies from psoriatic patients with or without itch and healthy volunteers as controls. The number of epidermal nerve fibres tended to increase in approximately 40% of psoriatic patients with itch compared with healthy controls, while such intraepidermal nerves were not observed in other itchy patients. In comparison with healthy controls, Sema3A levels also tended to decrease in the epidermis of psoriatic patients with itch. However, no relationship was found between nerve density and Sema3A levels in the epidermis of psoriatic patients with itch. The levels of μ-opioid receptor and β-endorphin in the epidermis were the same in healthy controls and psoriatic patients with or without itch. The levels of κ-opioid receptor and dynorphin A were significantly decreased in the epidermis of psoriatic patients with itch compared with healthy controls. Based on Sema3A levels in the epidermis, epidermal opioid systems, rather than hyperinnervation, may be involved in the pathogenesis of psoriatic itch.

Skin morphological analysis upon treatment with anti-TNF-alpha agents in psoriatic patients

Psoriasis is the most common immune-mediated skin disease worldwide, with an estimated incidence of about 2%. It is characterized by erythematous scaly plaques and its pathogenesis is mostly due to an interplay among epidermal cells, immunocompetent cells, and pro-inflammatory cytokines. Previous studies on psoriatic skin demonstrated delayed terminal differentiation, keratinocyte hyperproliferation, and abnormal occludin expression in tight junctions. However, evidences about desmosomal cadherin distribution in psoriatic patients are not available so far, and only scattered studies have been carried out on adherens junctions. In psoriasis, Tumor Necrosis Factor- alpha (TNF-alpha) plays a central role, strongly supporting the treatment with anti-TNF-alpha agents, but the effects of these agents on epidermal intercellular adhesion, terminal differentiation, and proliferation have still to be elucidated. In this preliminary study, we investigated by immunofluorescence the expression of transmembrane proteins in tight junctions (occludin), adherens junctions (E-cadherin), and desmosomes (desmocollin-1 and desmoglein-1) in normal (N=5) and psoriatic skin before/after treatment with anti-TNF-alpha agents (N=5). Differentiation biomarkers (keratin-10, keratin-14, and involucrin) and epithelial proliferation were also evaluated. In psoriatic epidermis occludin, keratin-14, and involucrin were expressed also in the spinous layer, differently from controls. Desmoglein-1, desmocollin-1, E-cadherin, and keratin-10 localizations were comparable in psoriatic and healthy subjects. Moreover, in all considered patients the hyperproliferative condition was accompanied by an unusual suprabasal distribution of replicating keratinocytes. Interestingly, the distribution pattern of all considered biomarkers of intercellular adhesion and terminal differentiation was reverted to the physiological condition upon treatment with anti-TNF-alpha agents. What’s more, the proliferative rate registered in anti-TNF-alpha treated patients was reduced and similar to controls, even though scattered suprabasal dividing cells were still present. Our results highlight that anti-TNF-alpha biologicals, next to their proven inhibitory action on the cytokinic pathway, are effective in restoring an efficient junctional apparatus, a more differentiated phenotype, and the typical proliferation rate in the epidermis of psoriatic patients.

Alterations in the distribution of intercellular junction proteins in the epidermis of psoriatic patients provide an insight of disease severity

Alterations in the distribution of intercellular junction proteins in the epidermis of psoriatic patients provide an insight of disease severity

Analysis of epidermal growth factor receptor gene in psoriasis.

Epidermal Growth Factor (EGF) plays an important role in cell proliferation. In psoriasis, increased histochemical expression of EGF receptor has been reported in the epidermis. In order to elucidate the mechanism of this increase, we studied the EGF receptor gene organization in psoriasis. DNAs were extracted from white blood cells of 5 patients with psoriasis and 5 normal controls and also from epidermis of 2 psoriatic patients and 1 normal control, and analyzed by Southern blot technique. There were no differences in the structural organization of EGF receptor gene in either white blood cells or epidermis between psoriatic patients and normal controls. These results suggest that the histochemical increase of EGF receptor in the epidermis of psoriatic patients is not due to a structural change in this gene.

Обнаружение экспрессии протоонкогенов в эпидермисе больных псориазом

Обнаружение экспрессии протоонкогенов в эпидермисе больных псориазом

Glycogen metabolism in psoriatic epidermis and in regenerating epidermis.

The observation that the glycogen content of epidermis from psoriatic lesions and from regenerating wound epithelium is increased has been confirmed by quantitative estimation. In epidermis from psoriatic lesions, although the proportion of glycogen synthase in the I form is only about 5% of the total and similar to control values, total glycogen synthase activity is increased approximately 4-fold and hence glycogen synthase I activity is increased to the same extent. In contrast, total phosphorylase activity is only slightly increased and, since the proportion of the enzyme in the a form is reduced, phosphorylase a activity is similar to control values. In epidermis from psoriatic lesions, the concentration of UDP-glucose is approximately doubled, and the concentrations of fructose 1,6-bisphosphate and of 6-phosphogluconate are increased approximately 5-fold. It is concluded that rates of glycogen synthesis, of glycolysis and of the pentose phosphate pathway are all enhanced in vivo and in consequence the rate of glucose uptake by psoriatic epidermis must be increased. In the non-involved epidermis of psoriatic patients the glycogen content is within normal limits, and although total glycogen synthase activity is increased the ratio of glycogen synthase I to phosphorylase a is maintained at normal levels by the appropriate phosphorylation of both enzymes. In regenerating wound epithelium in the pig, the changes in enzyme activity and in metabolite concentration closely resemble those found in epithelium from psoriatic lesions except that in wound epithelium the proportion of phosphorylase in the a form is increased relative to normal epithelium.