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Psoriasis is an immune-mediated disease, with genetic background and triggering environmental factors; however, several gaps are still present in understanding the intertwined relationship between these elements. Epigenetic mechanisms, including microRNAs (miRNAs), play an important role in the pathogenesis of psoriasis. The relationship between interleukin (IL)-17, a key cytokine in psoriasis, and these epigenetic mechanisms still needs to be elucidated. This study aimed at assessing the expression of miRNA-155, miRNA-210, and miRNA-20b in skin and sera of psoriasis patients in relation to IL-17 levels. For 20 psoriasis patients and 20 matching controls, the expression of miRNA-155, miRNA-210, and miRNA-20b was assessed using real-time polymerase chain reaction (RT-PCR), whereas IL-17/IL-17A levels were measured using quantitative enzyme-linked immunosorbent assay (ELISA) technique. MiRNA-155 expression was significantly higher in lesional skin compared to controls ( P  = 0.001). MiRNA-210 expression was significantly higher in both, lesional skin ( P  = 0.010) and sera of patients ( P  = 0.001) in comparison with controls. A statistically significant positive correlation was found between serum miRNA-210 expression and serum levels of IL-17/IL-17A ( P  = 0.010, rs = 0.562). MiRNA-20b lesional and non-lesional expression was significantly higher than controls ( P  < 0.001; P  = 0.018). In conclusion, the expression of miRNA-155, miRNA-210, and miRNA-20b is exaggerated in psoriasis and they may be involved in disease pathogenesis. A possible relationship between miRNA-210 and IL-17 may be suggested; however, further studies are still needed to verify this relation.

Adipose tissue is now considered an endocrine organ secreting different cytokines known as adipocytokines. Lipocalin-2 has been recently identified as an adipokine present in the circulation, it is related to insulin resistance, obesity, atherosclerotic diseases and type 2 diabetes. Lipocalin-2 and psoriasis are assumed to be closely associated with the metabolic syndrome. The aim of the present study is to estimate the level of lipocalin-2 in the serum and tissue of psoriatic patients and to correlate these levels with markers of metabolic syndrome, CRP and disease severity. This study was done on 30 patients of psoriasis and 30 healthy controls. All patients and controls were subjected to clinical examination. Serum, tissue levels of lipocalin-2 and C-reactive protein (CRP) were measured by enzyme linked immunosorbent assay technique. Metabolic syndrome parameters including anthropometric measures, lipid profiles, blood sugar and blood pressure were studied. Patients with psoriasis showed significant association with metabolic syndrome parameters than controls. Tissue lipocalin-2 was significantly higher than serum levels in psoriasis patients. A significant difference was detected in tissue levels of lipocalin-2 and not in the serum between patients and controls. Both tissue and serum lipocalin-2 correlated with CRP. Although there was a correlation between tissue and serum levels of lipocalin-2 in patients, there was no correlation between both of them with metabolic syndrome and related disorders. Our results revealed that patients with psoriasis are at increased risk of metabolic and cardiovascular complications, tissue lipocalin-2 is more specific to psoriasis than serum lipocalin-2. Lipocalin-2 has no role in determining severity of the disease. Neither tissue nor serum lipocalin-2 conveys cardiovascular risk in psoriasis patients.

Background: Growing evidence points to a causative relationship between altered activity of peroxisome proliferator-activated receptor γ (PPARγ) and psoriasis on the one hand, and its relationship with metabolic syndrome (MS) on the other., Objective: Could altered PPARγ levels be one of the culprits responsible for translating the metabolic state among psoriatic patients?, Materials and Methods: This investigational cross-sectional study included 60 psoriatics and 60 controls. Subjects were subgrouped according to the presence or absence of MS. Biopsies were taken from all subjects for immunohistochemical staining for PPARγ and western blot technique was carried out., Results: PPARγ immunostaining in psoriatics was significantly lower than in controls with the lowest levels documented in patients with MS (P<0.001). PPARγ immunostaining level was significantly lower in diabetics, hypertensive and insulin resistance patients (P<0.05). It also showed a significant positive correlation with high density lipoprotein (HDL) levels and significant negative correlation with age, psoriasis area and severity index (PASI), body mass index, and blood glucose levels. Similar results were obtained by western blot technique., Conclusion: Reduced PPARγ could be added to the factors responsible for translating the metabolic state among psoriatic patients. PPARγ agonists can present an adjuvant therapeutic tool in treatment of psoriatics with MS.

Background: Direct intercellular signaling, which controls keratinocyte behavior, proliferation and differentiation, occurs through gap junctions. Altered expression of connexins may play a role in the development of psoriatic lesions., Objectives: We estimated connexin 26 (Cx26) mRNA in psoriatic patients and investigated whether the standard therapeutic modalities (methotrexate and PUVA) exert their anti-psoriatic activity partially through altering Cx26 mRNA levels. We also detected Cx26 in skin biopsies by immunohistochemistry. RT-PCR measured Cx26 mRNA levels in 24 chronic plaque psoriasis patients. Group A received intramuscular methotrexate and group B was treated by PUVA for ten weeks, each followed by measurement of Cx26 mRNA levels and immunohistochemistry. Twelve healthy volunteers served as controls., Results: Cx26 mRNA expression was significantly higher in the patients before treatment than in controls (P<0.001). Post treatment levels were significantly lower than pre-treatment levels (P<0.001), however, significantly higher than in controls (P<0.001). Methotrexate and PUVA caused significant reductions in Cx26 mRNA expression (P=0.002, P=0.028 respectively). Post treatment levels were slightly significantly lower in the methotrexate group than in the PUVA group (P=0.046). The reduction in Cx26 mRNA expression was significantly positively correlated with the clinical improvement of the psoriatic plaque (P=0.002). Immunostaining of Cx26 decreased after treatment., Conclusion: Altered expression of the gap junction protein Cx26 may have a role in the development of the psoriatic phenotype. Both methotrexate and PUVA significantly lowered the expression of Cx26 mRNA and protein.

Background: The pathogenesis of psoriasis is thought to depend on the activation of immune cells and their secreted cytokines, chemokines and growth factors like IGF-1 which may contribute to the epidermal hyperplasia of psoriasis. Treatment of psoriasis with PUVA and methotrexate are associated with clinical improvement and decrease in epidermal hyperplasia., Objective: To examine the effects of PUVA and methotrexate therapy on IGF-1 expression in psoriatic plaques and whether this change correlates with clinical response., Methods: For 24 psoriatic patients, the PASI score and levels of lesional IGF-1 and its mRNA were determined by RT-PCR before and after treatment with either methotrexate or PUVA. Skin biopsies from 12 healthy volunteers served as control for IGF-1 levels in normal skin., Results: Lesional skin of psoriatic patients showed a statistically significant elevation in IGF-1 and its mRNA levels in comparison to control (P = 0.0001). Both methotrexate and PUVA treatment were associated with a significant decrease in both PASI scores and lesional IGF-1 after 10 month treatment., Conclusion: Both methotrexate and PUVA therapy for psoriasis are associated with a decrease in PASI score and IGF-1. The IGF-1 down-regulation may possibly be a consequence of the decrease in cytokines and inflammatory cellular infiltrate that occur following treatment with either modalities or due to their effect on local fibroblast activity and proliferation., (© 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.)

Peroxisome proliferator-activated receptor β/δ is a member of the nuclear hormone receptor superfamily suggested to contribute to psoriasis pathogenesis. Methotrexate and PUVA mainly target the T cell-mediated immunopathology of psoriasis. Our work aimed at estimating PPARβ/δ in psoriatic patients and investigating whether the standard therapeutic modalities (methotrexate and PUVA) exert their anti-psoriatic activity partially through altering PPARβ/δ levels. RT-PCR was used to measure PPAR β/δ mRNA levels in twenty four chronic plaque psoriasis patients. Patients were divided into two groups (12 patients each); group A received intramuscular methotrexate and group B was treated by PUVA 3 times/week in a PUVA 1000 cabin for ten weeks each, followed by measurement of PPAR β/δ mRNA levels. Twelve healthy volunteers served as controls. PPAR β/δ mRNA levels were significantly elevated in all patients and significantly decreased ten weeks after treatment, however, post treatment levels were still significantly elevated in comparison with those of controls. PPAR β/δ mRNA levels showed a significant positive correlation with disease duration.

Background: In psoriasis, keratinocyte hyperplasia may be explained by imbalance of growth factors responsible for epidermal proliferation and altered metabolism of their receptors. Transforming growth factor-beta 1 (TGF-beta1) implications in the pathogenesis of psoriasis can be attributed to several mechanisms besides keratinocyte cell cycle inhibition., Objectives: To evaluate the relation between serum and tissue levels of TGF-beta1 in psoriasis and their correlation with disease parameters., Patients and Methods: Serum and punch biopsy of involved and non-involved skin of 22 patients with psoriasis vulgaris and 10 controls were collected for quantification of TGF-beta1 by enzyme-linked immunosorbent assay kit., Results: Serum level of TGF-beta1 in psoriatic patients was higher than controls in a statistically non-significant manner. Correlations between serum level of TGF-beta1 and extent of the disease (P = 0.007) and Psoriasis Area and Severity Index (PASI) score (P = 0.005) were observed. Mean tissue levels of TGF-beta1 were highest in psoriatic lesions in contrast to normal skin of psoriatic patients and healthy controls, but not statistically significant. Correlation between tissue levels of TGF-beta1 in non-involved skin and extent of the disease (P = 0.007) and PASI score (P = 0.013) was detected. Correlation was detected between levels of TGF-beta1 in psoriatic plaques and serum of patients (P = 0.035), but not between levels of TGF-beta1 in non-involved skin and serum., Conclusions: Tissue expression of TGF-beta1 in psoriasis may be affected by the stage of development of the lesion. The direct relation between TGF-beta1 in psoriatic plaques and serum imply that the mechanisms for TGF-beta1 production and release in both these compartments may be related.