Psoriatic Skin Lesions Research Articles

Nucleotide binding and oligomerization domain 2 in psoriasis: a clinical and immunohistochemical study

ABSTRACT Psoriasis is a chronic immune-mediated inflammatory disease, affecting about 2 to 3% of the population worldwide. Nucleotide-binding and oligomerization domain 2-like receptor has been implicated in the pathogenesis of different inflammatory diseases. The current work aims to investigate the expression of nucleotide-binding and oligomerization domain 2-like receptor in psoriatic skin through an immunohistochemical study. This cross-sectional case-control study included 20 patients with chronic plaque psoriasis and 20 age- and sex-matched normal subjects as controls. Psoriasis severity was assessed through the use of Psoriasis Area Severity Index (PASI) score. Skin biopsies were taken under local anesthesia from cases and from matched sites of controls. Expression of nucleotide-binding and oligomerization domain 2 in epidermis of studied cases and controls showed positive epidermal expression of nucleotide-binding and oligomerization domain 2 in all cases (100%) versus 6 (30%) controls with a significant increase (χ2 = 21.54, P˂0.001). Moreover, dermal expression of nucleotide-binding and oligomerization domain 2 was higher in psoriatic skin lesion (95%) compared to controls (15%) with a significant difference (χ2 = 25.86, P˂0.001). We concluded that nucleotide-binding and oligomerization domain 2 may be implicated in psoriasis pathogenesis being higher in cases in comparison to controls.

Overexpression of Wilms tumor 1 promotes IL-1β expression by upregulating histone acetylation in keratinocytes

Psoriasis is a common inflammatory skin disease. Infiltration of inflammatory cells and excessive proliferation of keratinocytes are the histopathological markers of psoriasis. The transcription factor Wilms Tumor 1 (WT1) is overexpressed in several tumor types, and plays an important part in the proliferation and apoptosis of cells. Studies have found that, compared with normal skin, WT1expression in the skin lesions of patients with psoriasis are increased significantly. Knockdown of WT1 inhibited the proliferation of a human epidermal keratinocyte cell line (HaCaT cells) and promoted their apoptosis, whereas WT1 overexpression exhibited the opposite effect. WT1 was overexpressed or inhibited in HaCaT cells by transfection with the WT1 plasmid or WT1 small interferring RNA (siRNA) using Lipofectamine 2000. Transcriptome sequencing and bioinformatics analysis revealed significant differences in IL-1β expression between the experimental group and control group. Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assays showed that expression of IL-1β and WT1 were consistent. Subsequently, IL-1β was demonstrated to be a target of WT1 by chromatin immunoprecipitation (ChIP)-sequencing and luciferase reporter assay. ChIP-qPCR showed that WT1 regulated IL-1β expression by altering acetylation. Expression of WT1 mRNA was positively correlated with expression of IL-1β mRNA in psoriatic skin lesions. Our study suggested that WT1 likely promotes psoriasis development by regulating its target gene IL-1β, which shows high expression in psoriatic lesions and is involved in psoriasis development. These findings provide a new target for psoriasis treatment.

Valosin-containing Protein in Psoriasis: A Clinical and Immunohistochemical Study.

Psoriasis is a chronic immune-mediated inflammatory skin disease, affects about 2% to 3% of the world population. Valosin-containing protein (VCP) is one of the newly discovered markers that is highly expressed in neoplasms and hyperproliferative lesions. This work aimed to study the role of VCP in psoriasis vulgaris by immunohistochemical study and correlate its expression with the available clinicopathologic data. This prospective case-control study was conducted on 25 patients with psoriasis vulgaris and 25 age-matched and sex-matched healthy individuals as a control group. Skin biopsies were taken under local anesthesia from cases and controls. VCP immunoreactivity showed that epidermal VCP expression had a significant stepwise increase (P=0.002) from control to lesional psoriatic sections. Epidermal VCP H-score was significantly associated with the progressive course (P=0.037). Similarly, VCP in the dermis showed a significant expression in lesional psoriatic skin (P≤0.001). Higher VCP in the dermis in cases with a history of joint affection (P<0.05) was detected. We concluded that VCP is a promising marker for follow-up and monitoring of psoriatic patients and may play a role as a therapeutic target.

BOOSTING THE SKIN DELIVERY OF CURCUMIN THROUGH STEARIC ACID-ETHYL CELLULOSE BLEND HYBRID NANOCARRIERS-BASED APPROACH FOR MITIGATING PSORIASIS

Objective: Curcumin presents poor topical bioavailability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of psoriasis. The present study reports the utilization of lipid-polymer hybrid nanoparticles (LPHNPs) for the topical delivery of curcumin which can be a potential approach for mitigating psoriasis.&#x0D; Methods: Curcumin-loaded LPHNPs were prepared by the emulsification solvent evaporation method and characterized. The optimized Curcumin-loaded LPHNPs (DLN-3) were further incorporated into 2% Carbopol 940 gels and evaluated for its therapeutic efficacy in the Imiquimod (IMQ)-induced psoriasis rat model.&#x0D; Results: The average particle size, polydispersity index, zeta potential, drug entrapment and loading efficiency for DLN-3 were found to be 200.9 nm, 0.342,-28.3 mV, 87.40±0.99% and 4.57±0.04%, respectively. FT-IR, DSC and XRD studies confirmed that all the components used for the formulation are compatible with each other, whereas SEM and TEM analysis affirmed the spherical shape of LPHNPs with a smooth surface. The in vitro drug release studies suggest that curcumin was released from the LPHNPs in a sustained manner over a period of 24 h via super case II transport mechanism. Results of in vitro skin permeation study revealed that 38.39±2.67% of curcumin permeated at 12 h across excised pig ear skin with a permeation flux of 18.74±3.59 µg/cm2/h. Further, in vivo evaluation and histopathological studies demonstrated that NLHG-1 hydrogels showed better therapeutic efficacy against the psoriatic skin lesions than the standard marketed gels.&#x0D; Conclusion: These results suggest that the developed LPHNPs have a superior ability to improve the skin penetration or accumulation of DLN-3 within psoriatic skin and offer a potential delivery system for the management of psoriasis.

MANAGEMENT OF MAGGOT INFLICTED WOUND – AYURVEDIC APPROACH

Unhygienic conditions attract organisms into the pathological lesion and worsen the condition, here is a case wherein the patient with psoriatic skin lesions took treatment from an unqualified person and in addition his unhygienic habit attracted maggots into the foot eating away a major chunk of his normal tissues. The case was diagnosed and treated in lines with fundamental principles of Sushruta. The case is a best example of maggots destructive and repair effect on the tissue, the wound with maggots presence healed faster than with wound without maggots.

Ebosin Ameliorates Psoriasis-Like Inflammation of Mice via miR-155 Targeting tnfaip3 on IL-17 Pathway.

Psoriasis is a recurrent autoimmune skin disease with aberrant regulation of keratinocytes and immunocytes. There is no universally accepted single treatment available for psoriasis, and the establishment of a common treatment option to control its signs and symptoms is urgently needed. Here, we found Ebosin, a novel exopolysaccharide isolated from Streptomyces sp. 139 by our lab, not only could ameliorate inflammation in LPS-induced keratinocytes through IKK/NF-kapaB pathway, but also attenuate psoriatic skin lesions and reduce inflammatory factors expression in imiquimod (IMQ)-mediated psoriatic mice. Except for inhibiting the expression of epidermal differentiation related proteins, Ebosin significantly increased the percentage of CD4+Foxp3+CD25+ Tregs and decreased CD4+IL17A+ Th17 cells in psoriatic mice. Furthermore, we demonstrate that Ebosin significantly suppressed the IL-17 signaling pathway via A20 (encoded by tnfaip3) in vivo. As the direct binding of tnfaip3 to miR-155 has been demonstrated by luciferase reporter assay, and Ebosin has been demonstrated to inhibit miR-155 level in vitro and in vivo, our study first indicates that Ebosin reduces inflammation through the miR-155-tnfaip3-IL-17 axis and T cell differentiation in a psoriasis-like model. Thus, we conclude that Ebosin can act as a promising therapeutic candidate for the treatment of psoriasis.

Discontinuation of infliximab in patients with ulcerative colitis in remission (HAYABUSA): a multicentre, open-label, randomised controlled trial

Anti-tumour necrosis factor (TNF) agents are the mainstay of long-term treatment for refractory ulcerative colitis. However, long-term use of anti-TNF therapy might lead to an increased risk of malignancy or infection. To date, no randomised controlled trial has evaluated whether anti-TNF agents can be safely discontinued in patients with ulcerative colitis in remission. We therefore aimed to compare outcomes in these patients who continued infliximab with those who discontinued infliximab. We did a multicentre, open-label randomised controlled trial at 24 specialist centres in Japan. We enrolled patients with ulcerative colitis who were in remission, had been treated with intravenous infliximab (5 mg/kg) every 8 weeks, and had started infliximab at least 14 weeks before study enrolment. No restrictions regarding age and comorbidities were used to exclude participation. Patients who were confirmed to be in remission for more than 6 months, to be corticosteroid-free, and to have a Mayo Endoscopic Subscore (MES) of 0 or 1 were centrally randomised. An independent organisation randomly assigned patients (1:1) into either the infliximab-continued group or infliximab-discontinued group, using a computer-generated stratified randomisation procedure. The stratified factors were the use of immunomodulators (yes or no) and MES (0 or 1). Neither patients nor health-care providers were masked to the randomisation. The primary endpoint was the remission rate at week 48 in the full analysis set, which was based on the intention-to-treat principle and excluded participants with no efficacy data after randomisation. This study was registered with the University Hospital Medical Information Network Center Trials registry, UMIN000012092. Between June 16, 2014, and July 28, 2017, 122 patients were eligible for screening and a total of 95 patients were randomly assigned to the infliximab-continued group (n=48) or the infliximab-discontinued group (n=47). 92 patients (n=46 for both groups) were included in the full analysis set. 37 (80·4% [95% CI 66·1-90·6]) of 46 patients in the infliximab-continued group and 25 (54·3% [39·0-69·1]) of 46 patients in the infliximab-discontinued group were in remission at week 48. The between-group difference was 26·1% (95% CI 7·7-44·5; p=0·0076) before adjustment and 27·3% (95% CI 8·0-44·1; p=0·0059) after adjustment for stratification factors. Eight (17%) of 48 patients in the infliximab-continued group and six (13%) of 47 in the infliximab-discontinued group developed adverse events (between-group difference 3·9% [95% CI -10·3 to 18·1]; p=0·59). In the infliximab-continued group, one patient had an infusion reaction and two patients had psoriatic skin lesions. Eight (66·7%, 95% CI 34·9-90·1) of the 12 patients in the infliximab-discontinuation group who were re-treated with infliximab after relapsing were in remission within 8 weeks of re-treatment; none had infusion reactions. Maintenance of remission was significantly more common in patients who continued infliximab than in those who discontinued. Discontinuing infliximab should therefore be discussed with caution, taking both risk of relapse and efficacy of re-treatment into account. Mitsubishi Tanabe Pharma Corporation and the Intractable Disease Project of the Ministry of Health, Labour and Welfare of Japan. For the Japanese translation of the abstract see Supplementary Materials section.

176 Transethnic analysis of psoriasis susceptibility in South Asians and Europeans enhances fine-mapping in the MHC and genomewide

We performed a GWAS of psoriasis in 2,590 cases and 1,720 controls of South Asian descent (SAS). Compared to our existing European-origin (EUR) GWAS, the effect sizes of known psoriasis signals were highly correlated in SAS and EUR (Spearman r = 0.78; p < 2 x 10−14). We then conducted a transethnic meta-analysis, identifying two novel non-MHC psoriasis loci (1p36.22 and 1q24.2). rs2103876 (1p36.22) is a cis-eQTL in blood for MTHFR, whose expression is positively correlated (p=4.2x10−97) with the psoriasis risk allele (T) and overexpressed in psoriatic lesional (PP) skin (p=3.06x10−23; FC =1.7). The only significant blood eQTL target for rs12046909 (1q24.2) is XCL1, a chemokine receptor ligand that is also overexpressed in PP skin (p=0.011; FC=1.95). For these two loci, the transethnic GWAS provided higher genetic resolution (mean reduction in 95% CI= 20 kb) and a reduction in the number of potential causal variants (mean = 10) than EUR alone. We explored multiple strategies to develop reference panels for accurately imputing MHC genotypes in both SAS and EUR. HLA-C*06 was the top-ranking MHC locus in both populations but was even more prominent in SAS. Transethnic modeling also substantially boosted the probability that HLA-C*06 is causal. Analysis of the extended MHC region uncovered 5 independent psoriasis loci in SAS, 14 in EUR, and 17 in transethnic, all of which map to the classical MHC. Secondary MHC signals included coding variants of HLA-C and HLA-B, but also potential regulatory variants of these two genes as well as HLA-A and several HLA class II genes, with effects on both chromatin accessibility and gene expression. This study highlights the value of transethnic meta-analysis for discovery and fine-mapping of susceptibility loci.

Hypertension due to loss of water

In the current issue of Acta Physiologica, two papers are published investigating the development of arterial hypertension under conditions of pathological loss of free water in two disease models. Kovaric et al 1 studied rats with chronic renal failure, shedding excessive free water via their remnant kidney due to a hypostenuric concentrating defect. Wild et al. 2 investigated a transgenic mouse model for psoriasis, losing free water via the psoriatic skin lesions. In both cases the animals displayed hypertension, cutaneous vasoconstriction, and metabolic adaptations towards enhanced production of urea and organic osmolytes typical for a phylogenetically ancient water conservation response termed aestivation 3 . The international consortia of investigators spearheaded by Titze, Karbach, and Kitada therefore conclude that in both cases the hypertension was due to cutaneous vasoconstriction in an attempt to limit epidermal water loss. Because in either case the hypertension was associated with loss of water, and thus with hypo- rather than hypervolemia, the authors argue, that this concept of pathogenesis of hypertension is antipodal to the classic view that relies on hypervolemia due to sodium retention.

Vasculature in the Margin of the Psoriatic Lesion

Background: Factors initiating capillary conversion in the immunopathogenesis of psoriasis are not well established and quantification of vascular changes in- and outside visible psoriatic plaque has not been studied extensively. Objectives: To assess the pathological involvement of capillaries in the context of well-established features of psoriasis in different phases: symptomless psoriatic skin distant from a lesion (SDL), adjacent to a lesion (SAL), the margin zone of the lesion (ML) and the center of the psoriatic lesion (CL). Methods: In 10 patients with chronic plaque psoriasis, and 10 healthy matched controls, vascular parameters (vascular tonicity (VD), vascular surface area (VAR), microvascular density (MVD), angiogenesis (pEC)) and hypoxia in the context of well-established features (keratinocyte proliferation, neutrophils and T-cells) were analyzed within the psoriatic lesion and symptomless psoriatic skin, using immunohistochemical markers (Ki67/CD31 double-staining and HIF-1α-, Elastase- and T-Bet-staining). Results: VD and neutrophils were significantly increased in all sites, compared to healthy controls. The VAR, MVD, Ki67+ nuclei, HIF-1α and T-Bet start to augment in the SAL. Within the overt psoriatic plaque angiogenesis increases. Biopsies closer to the center of a plaque, exhibited increased values of the MVD, VAR, VD, Ki67+ nuclei, T-Bet+ Th1 cells and neutrophils. Conclusion: In SDL, vasodilatation and activation of the innate immune system (increased neutrophils) was detected. This could indicate that psoriasis is not restricted to lesional skin, but rather is a systemic disease. Closer to the psoriatic plaque, vascular and epithelial proliferation was observed, along with hypoxic cells and activation of the acquired immunity (augmented T-Bet cells).

A case study on psoriasis

Psoriasis is a non-contagious, chronic skin condition that produces plaques of thickened, scaling skin. The dry flakes of skin scales result from the excessively rapid proliferation of skin cells. Psoriasis is generally thought to be a genetic disease which is triggered by environmental factors. Psoriasis is estimated to affect 2-4% of the population of the western world. The rate of psoriasis varies according to age, region and ethnicity; a combination of environmental and genetic factors is thought to be responsible for these differences. Psoriasis affects both sexes equally. It can occur at any age, although it most commonly appears for the first time between the ages of 15 and 25 years. Approximately one third of people with psoriasis reports being diagnosed before age 20. In India the prevalence of psoriasis varies from 0.44 to 2.8%, it is twice more common in males compared to females, and most of the patients are in their third or fourth decade at the time of presentation. In addition to the appearance and distribution of the rash, specific medical signs may be used by medical practitioners to assist with diagnosis. These may include Auspitz's sign (pinpoint bleeding when scale is removed), Koebner phenomenon (psoriatic skin lesions induced by trauma to the skin), Candle grease sign and itching and pain localized to papules and plaques. A patient of sixty five years old was suffering from Psoriasis for last 12 years resorted to all systems of treatment but failed, was finally treated by constitutional treatment and was cured for last 5 years. The case taking was done in a standardized format and all symptoms were passed through standard procedures to arrive at totality of symptoms such as analysis of symptoms, conceptual image, analysis of the case/ synthesis, reportorial totality/ evolutional totality, miasmatic diagnosis, repertorisation. The medicine was prescribed in 50 millesimal scale in infrequent repetition scheduled. Change of potency and medicine were done as per the guidelines of tenets of Homoeopathy and cure was achieved to an intractable chronic disease like Psoriasis.

Proteomic analysis of psoriatic skin lesions in a Chinese population

Psoriasis is a chronic skin disorder with undefined pathogenesis. Several biomarkers for this disease have been identified by proteomic analysis. We explored the whole-proteomic changes in 45 pairs of psoriatic and adjacent noninvolved skin tissues in a Chinese population. A total of 3686 proteins were identified, of which 3008 were quantified. A total of 102 and 124 proteins were upregulated and downregulated in lesional skin, respectively. SART1 (P = 3.55 × 10−5) and GLTP (P = 1.54 × 10−3) were the most significantly down- and upregulated proteins. Nearly 90% of these differentially regulated proteins exhibited the same expression trends as those in an online RNA sequencing dataset for psoriasis; 19 differentially regulated proteins exhibited a negative relationship with DNA methylation data for psoriatic lesions. The differentially expressed proteins were enriched in ribosomes, antigen processing and presentation, immune response, and IL-17 signalling pathways. This study identified multiple differentially regulated proteins in psoriatic lesions, which suggested that changes in the proteome play important regulatory roles in psoriasis-associated processes. SignificanceProteomic analysis was performed in 45 pairs of psoriatic and adjacent noninvolved skin tissues in a Chinese population. More than 3000 proteins were quantified, of which 226 were differentially expressed in psoriatic skin tissues. These proteins were mainly enriched in the immune response, antigen processing and presentation and IL-17 signalling pathways, which have been reported to be associated with the pathogenesis of psoriasis.

Differential Changes in Inflammatory Mononuclear Phagocyte and T-Cell Profiles within Psoriatic Skin during Treatment with Guselkumab vs. Secukinumab

Cellular sources of IL-23 and IL-17A driving skin inflammation in psoriasis remain unclear. Using high-dimensional unsupervised flow cytometry analysis, mononuclear phagocytes and T cells were examined in the same lesions of patients before and during guselkumab (IL-23p19 blocker) or secukinumab (IL-17A blocker) treatment. Among CD11c+HLA-DR+ mononuclear phagocytes, CD64brightCD163-CD14brightCD1c-CD1a‒ inflammatory monocyte‒like cells were the predominant IL-23-producing cells and, together with CD64-CD163-CD14-IL-23p19-TNF-α+ inflammatory dendritic cell‒like cells, were increased in lesional compared with those in nonlesional skin taken from the same patient. Within T cells, CD8+CD49a+ and/or CD103+ tissue-resident memory T cells, CD4+CD25+FoxP3+ regulatory T cells, and CD4+CD49a-CD103- T cells were increased. Moreover, CD4+CD49a-CD103- T cells and the relatively rare CD8+ memory T cells equally contributed to IL-17A production. Both treatments decreased the frequencies of inflammatory monocyte‒like, inflammatory dendritic cell‒like, and CD4+CD49a-CD103- T cells. In contrast, guselkumab reduced memory T cells while maintaining regulatory T cells and vice versa for secukinumab. Neither drug modified the frequencies of IL-17A+IL‒17F+/- CD4+ or CD8+ T cells. This study reveals the identity of the major IL-23+ mononuclear phagocyte and IL-17+ T-cell subsets in psoriatic skin lesions and paves the way for a better understanding of the mode of action of drugs targeting the IL-23/IL-17A pathway in psoriasis.

Role of CYR61 in psoriatic lesional and perilesional skin: A clinical and immunohistochemical study.

Psoriasis is considered as an immune-mediated disorder with significant epidermal hyperplasia and inflammation. Cysteine-rich angiogenic inducer 61 (CYR61), known as CCN family member 1 (CCN1), plays an important role in cell proliferation and neovascularization which may trigger psoriasis development. This study aimed to assess the immunostaining of CYR61 in psoriatic skin (lesional and perilesional) compared to control skin. This is a case-control study. The Psoriasis Area and Severity Index (PASI) was used to evaluate disease severity. A punch biopsy was taken from psoriatic skin lesions (30), perilesional (30) skin, and matched site of controls (20). The pathological and immunostaining assessments of CYR61 were conducted. There was a significant gradual progressive overexpression of CYR61 in keratinocytes from control skin to perilesional and lesional psoriatic skin (P=.00). Moreover, lesional psoriatic skin showed overexpression of CYR61 in inflammatory cells in the dermis than controls. CYR61 expression (lesional epidermis) revealed a significant positive correlation with the PASI score (r=.63; P=.00). There was a significant relationship between intensity and H-core of CYR61 in the lesional psoriatic epidermis with joint affection. CYR61 may trigger epidermal hyperplasia and potentiate inflammatory infiltration in psoriasis vulgaris patients, and therapies targeting CYR61 may be effective in the management of psoriasis vulgaris.

Distribution of Malassezia species on the skin of patients with psoriasis

IntroductionMalassezia species can induce the expression of interleukin-17 (IL-17), which plays an important role in the inflammatory and immune response in psoriasis (PS). The purpose of this study was to investigate the Malassezia species composition in patients with PS and healthy individuals and explore the role of Malassezia species in the pathogenesis of PS. Materials and methodsA total of 28 patients with PS and 10 age- and sex-matched healthy individuals participated in this study. Specimens collected from the lesional and non-lesional skin of patients with PS and the skin of healthy individuals were analyzed by using nested PCR. ResultsThe relative abundance of Malassezia species was 84.96% in healthy subjects, more than twice that in patients with PS (P<0.01). M. restricta (43.09%) and M. globosa (41.38%) were the main Malassezia species in patients with PS followed by M. furfur (4.84%) and M. sympodialis (2.49%). M. sympodialis accounted for 18. 81% of the Malassezia species in healthy subjects, which was nearly eight times higher than in patients with PS (P<0.01). Further, M. furfur was detected both on lesional and non-lesional psoriatic skin, but it was not found on the skin of healthy individuals. ConclusionsThe Malassezia species composition in patients with PS differed from that of healthy individuals. M. restricta and M. globosa were the main Malassezia species in patients with PS.

DZ2002 alleviates psoriasis-like skin lesions via differentially regulating methylation of GATA3 and LCN2 promoters

Psoriasis is the most prevalent inflammatory skin disorders, affecting 1–3% of the worldwide population. We previously reported that topical application of methyl 4-(adenin-9-yl)-2-hydroxybutanoate (DZ2002), a reversible S-adenosyl-l-homocysteine hydrolase (SAHH) inhibitor, was a viable treatment in murine psoriatic skin inflammation. In current study, we further explored the mechanisms of DZ2002 on keratinocyte dysfunction and skin infiltration, the key pathogenic events in psoriasis. We conducted genome-wide DNA methylation analysis in skin tissue from imiquimod (IMQ)-induced psoriatic and normal mice, demonstrated that topical administration of DZ2002 directly rectified aberrant DNA methylation pattern in epidermis and dermis of psoriatic skin lesion. Especially, DZ2002 differentially regulated DNA methylation of GATA3 and LCN2 promoters, which maintained keratinocytes differentiation and reduced inflammatory infiltration in psoriatic skin respectively. In vitro studies in TNF-α/IFN-γ-elicited HaCaT manifested that DZ2002 treatment rectified compromised keratinocyte differentiation via GATA3 enhancement and abated chemokine expression by reducing LCN2 production under inflammatory stimulation. Chemotaxis assays conducted on dHL-60 cells confirmed that suppression of LCN2 expression by DZ2002 was accompanied by CXCR1 and CXCR2 downregulation, and contributed to the inhibition of CXCL8-driven neutrophils migration. In conclusion, therapeutic benefits of DZ2002 are achieved through differentially regulating DNA methylation of GATA3 and LCN2 promoters in psoriatic skin lesion, which efficiently interrupt the pathogenic interplay between keratinocytes and infiltrating immune cells, thus maintains epidermal keratinocytes differentiation and prevents dermal immune infiltration in psoriatic skin.

Down-regulation of miR-155 after treatment with narrow-band UVB and methotrexate associates with apoptosis of keratinocytes in psoriasis.

Psoriasis is a chronic inflammatory skin disease arising from a complex interaction between genetics, epigenetics, the host's immune system and the environment. Recent accumulated data revealed the dysregulation of various microRNAs (miRNAs) in several diseases including psoriasis. We explored the functional role and regulation of hsa-miR-155-5p (miR-155) in an immortalized keratinocyte cell line (HaCaT), in relation to the pathogenesis and treatment of psoriasis. miR-155 expression in normal skin and psoriatic skin lesion before and after treatment with methotrexate (MTX) and narrow-band ultraviolet B phototherapy (NB-UVB) were analyzed using quantitative reverse transcription PCR (qRT-PCR). Apoptotic activity, cell cycle and viable cells of miR-155 transfected HaCaT were measured using flow cytometry and MTS assay. Since, caspase-3 (CASP3) gene was predicted as a target gene of miR-155, the expression of CASP3 was detected in transfected HaCaT using western blot. We discovered that both MTX and NB-UVB significantly down-regulated miR-155 expression in psoriatic skin lesions. We also found that overexpression of miR-155 in HaCaT led to suppression of cell apoptosis and induced cell arrest at G0/G1 phase. Moreover, CASP3 expression was down-regulated in miR-155 transfected HaCaT. This study demonstrates down-regulation of miR155 after treatment with MTX and NB-UVB in psoriatic skin lesion. miR155 plays significant role in apoptosis on HaCaT via CASP3. This finding provides a better understanding of the pathogenesis of psoriasis and might aid on developing the new monitoring tool or therapy for psoriasis in the future.

Expression of liver X receptor-α in lesional and perilesional skin in patients with psoriasis vulgaris

Background Psoriasis is a common chronic recurrent immune-mediated disease of the skin. Liver X receptor-alpha (LXR-α) is a member of the nuclear receptor family of transcription factors. LXR-α was found to be expressed in the skin. Objective To assess immunohistochemical expression of LXR-α in psoriatic (perilesional and perilesional) skin compared with control and to correlate its expression with the clinical and histopathological parameters of that disease in the studied patients. Patients and methods This case–control study was carried out on 76 participants, including 38 patients having chronic plaque psoriasis, besides 38 age-matched and sex-matched apparently normal volunteers (control group). The severity of psoriasis was assessed by Psoriasis Area and Severity Index score. The skin biopsies were subjected to hematoxylin and eosin and immunohistochemical staining of LXR-α. Results There was a significant stepladder downregulation of LXR-α from control to perilesional psoriatic skin, ending with lesional psoriatic skin, regarding its expression and H score in epidermis and dermal elements (P<0.001 for all). In the dermis, LXR-α topography was cytoplasmic in all psoriatic (perilesional and lesional) skin sections (100%) versus 22.2% in controls, where it was nucleocytoplasmic in 28 (77.8%) sections. Moreover, epidermal keratinocytes LXR-α demonstrated cytoplasmic localization in nearly all psoriatic sections (100% lesional and 90.9% perilesional) versus 18.9% controls (P<0.001). Conclusion Decreased LXR-α in psoriatic tissue may participate actively in psoriasis. LXR-α agonist may be of value in psoriasis management program.

Immunohistochemical Expression of p53 and bcl-2 in Psoriasis

Introduction: Apoptosis plays a major role in maintaining the balance between cellular proliferation and cell death in the skin. Blockage of apoptosis has been implicated as one of the contributing factors in the pathogenesis of psoriasis. P53 has a role in induction of cell cycle arrest, apoptosis as well as regulation of cell proliferation, bcl-2 is anti-apoptotic protein. Previous studies have reported controversial results relating to their expression in psoriatic skin. Aim: To evaluate the immunohistochemical expression of p53 and bcl-2 in the epidermis, basal cells and lymphocytes of psoriatic skin and compare it with the adjacent perilesional skin. Materials and Methods: This cross-sectional study was conducted in Hind Institute of Medical Sciences, Safedabad, Barabanki, Uttar Pradesh, India from June 2016 to December 2017. Fifty cases of psoriasis were included and punch skin biopsies including a small part of perilesional skin was taken. The sections were studied for the presence of immunohistochemical expression of p53 and bcl-2 using scoring systems. The perilesional part of the biopsy was used for comparing the histopathological and immunohistochemical expressions. The student t-test was used for comparison of groups using Statistical Package for the Social Sciences (SPSS) version 23.0 program and a p-value of &lt;0.05 was taken as statistically significant. Results: The age of the patients ranged from 15-68 years. Majority of the patients were males comprising 32 out of 50 cases (64%). The most common site was the extensor surfaces of limbs. The histopathological findings of psoriasis, such as acanthosis, spongiosis, suprapapillary thinning, dilated dermal vessels and dermal lymphocytic infiltrate was seen in all 50 cases of the lesional skin (100%). Dermal lymphocytic infiltrate was the most common finding in the perilesional skin and was observed in 21 cases (42%). Statistically significant immunohistochemical expression of p53 was seen chiefly in the epidermis, while bcl-2 expression was seen in the dermal lymphocytes of psoriatic (lesional) skin. Conclusion: The immunohistochemical expression of p53 in the epidermal keratinocytes of the lesional skin in psoriasis is suggested to be of wild type in response to frequent DNA damage in the actively cycling cells of epidermis. The expression of bcl-2 in the dermal lymphocytes could point towards its role in promoting the chronic inflammatory and recurrent nature of psoriatic lesions.

Aryl Hydrocarbon Receptor and Autophagy-Related Protein Microtubule-Associated Protein Light Chain 3 Expression in Psoriasis.

BackgroundThe aryl hydrocarbon receptor (AHR) and autophagy are both important to maintain skin homeostasis. However, they are also involved in skin disorders. So far, their roles in psoriasis pathogenesis are unknown.ObjectiveWe studied the immunohistochemical and gene expression of AHR, CYP1A1, and microtubule-associated protein light chain 3 (LC3) in lesional skin of psoriasis patients to determine correlations among them.MethodsWe included 24 psoriasis patients and ten healthy volunteers. Skin biopsies were collected. AHR, CYP1A1, and LC3 protein expression was examined by immunohistochemistry, immunofluorescence, and western blotting. AHR, CYP1A1, LC3, ATG5, BECN1 and Nrf2 mRNA levels were measured by quantitative polymerase chain reaction.ResultsAHR and CYP1A1 protein expression were higher in psoriasis lesional skin than in normal skin. LC3 protein expression was lower in psoriasis lesions than in normal controls. AHR and CYP1A1 protein expression in psoriasis lesions showed significant positive correlations with mean epidermal thickness and inflammatory cell density. Significant negative correlations were noted between LC3 protein expression in psoriasis lesions and the mean epidermal thickness or inflammatory cell density. A significant negative correlation was found between AHR and LC3 expression in psoriatic skin. AHR, CYP1A1 and Nrf2 mRNA expression were upregulated while LC3, ATG5, and BECN1 mRNA were down-regulated, in psoriatic lesional skin compared with normal controls.ConclusionAHR and autophagy could play a role in psoriasis pathogenesis by modifying epidermal hyperproliferation and inflammation. AHR and autophagy regulation are potential therapeutic targets in chronic inflammatory skin diseases.