Evidence for biochemical barrier restoration: Topical solenopsin analogs improve inflammation and acanthosis in the KC-Tie2 mouse model of psoriasis
Jack L. ArbiserRon NowakKellie A. MichaelsYuliya SkabytskaTilo BiedermannMonica J. LewisMichael Y. BonnerShikha RaoLinda GilbertNabiha YusufIsabella KarlssonYi FritzNicole L. Ward
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Abstract Psoriasis is a chronic inflammatory skin disease affecting 2.5–6 million patients in the United States. The cause of psoriasis remains unknown. Previous human and animal studies suggest that patients with a susceptible genetic background and some stimulus, such as barrier disruption, leads to a coordinated signaling events involving cytokines between keratinocytes, endothelial cells, T cells, macrophages and dendritic cells. Ceramides are endogenous skin lipids essential for maintaining skin barrier function and loss of ceramides may underlie inflammatory and premalignant skin. Ceramides act as a double-edged sword, promoting normal skin homeostasis in the native state, but can be metabolized to sphingosine-1-phosphate (S1P), linked to inflammation and tumorigenesis. To overcome this difficulty, we synthesized solenopsin analogs which biochemically act as ceramides, but cannot be metabolized to S1P. We assess their in vivo bioactivity in a well-established mouse model of psoriasis, the KC-Tie2 mouse. Topical solenopsin derivatives normalized cutaneous hyperplasia in this model, decreased T cell infiltration, interleukin (IL)-22 transcription, and reversed the upregulation of calprotectin and Toll-like receptor (TLR) 4 in inflamed skin. Finally, they stimulated interleukin (IL)-12 production in skin dendritic cells. Thus suggesting barrier restoration has both a biochemical and physical component, and both are necessary for optimal barrier restoration.Keywords:
Barrier function
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Drug ingestion may play an important role in the induction and exacerbation of psoriasis. Drugs may directly induce the occurrence of psoriasis in susceptible individuals, or cause the recurrence or exacerbation of preexisting psoriasis. In view of their relationship with psoriasis, drugs can be classified as follows: drugs that are definitely able to induce or exacerbate psoriasis (e.g., lithium), and drugs that are possible to induce or exacerbate psoriasis (e.g., interferon). Clinical and histological studies on drug-induced or-exacerbated psoriasis are helpful to investigate into the pathogenesis of psoriasis. Further studies are still needed for drugs that are possible to induce or exacerbate psoriasis, which may be of great importance for the prevention of psoriasis in susceptible individuals.
Key words:
Psoriasis; Pharmaceutical preparations; Lithium compounds; Antimalarials; Biological agents; Provoke; Exacerbate
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Objective To Investigate whether the PDEs activities is abnormal or not in psoriasis patients by detecting the PDEs activities of both psoriasis patients and healthy controls, and explore the potential role of PDEs activities changes in the pathogenesis of psoriasis. Methods PDEs activities were detected by using high performance liquid chromatography(HPLC) in 50 patients with psoriasis and 60 healthy controls. Results The PDEs activities is 10.40%±3.54% in psoriasis patients,and 8.60%±2.25% in the healthy controls. The PDEs activities in patients with psoriasis is significant higher than that in the controls (P0.05). Conclusions The PDEs activities may be a risk factor for psoriasis.
Pathogenesis
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Psoriasis is a chronic, immune-mediated, inflammatory disorder characterized by erythema, redness, thickening, and scaling of the skin. Psoriasis is caused by the accelerated keratinocyte cell proliferation and dysregulation of the immune system. The cause of psoriasis is unknown, but it can be a genetic component. Several factors are thought to aggravate psoriasis. These include stress, excessive alcohol consumption, and smoking. The concept of the pathogenesis of psoriasis is based on the proliferation and differentiation of keratinocytes, recent studies have proved that the dysregulation of the immune system plays a critical role in the development of psoriasis. Immune cells release T cells, keratinocytes, neutrophils, and the cytokines, have a specific interaction with each other that is the core mechanism of the development of psoriasis. Trigger factors of psoriasis is also genetic, environmental and behavioral factors. The prevalence of psoriasis is estimated to range from 0.91% to 8.5% worldwide in adults. Clinically, psoriasis vulgaris is the most common subtype of psoriasis and affects approximately 90% of patients.
Immune Dysregulation
Pathogenesis
Erythema
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Sun Exposure
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Interleukin 20
Interleukin 3
BETA (programming language)
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【Objectives】 To test the expression levels of soluble CD147(sCD147) in plasma of psoriasis vulgaris(PV) patients and normal controls. Describe disease severity of PV with psoriasis lesion degree score(PASI) and analyze the correlation between the expression levels of sCD147 in psoriasis patients and disease severity. To test the expression levels of sCD147 in plasma of different subtypes of psoriasis patients, and study the roles of sCD147 play in the psoriasis classification. 【Methods】 Detect the expression levels of sCD147 in 74 PV patients and 41 normal controls by enzyme-linked immunosorbent assay(ELISA). Analyze the correlation between sCD147 expression levels and PASI score. Detect the expression levels of sCD147 of plasma in 10 patients with psoriasis pustulose(PP), 12 patients with arthritis psoriasis(PsA) and 7 patients with psoriasis erythrodermic(PE). Statistical analyze the difference of sCD147 expression levels in patients with different subtypes of psoriasis. 【Results】 The sCD147 expression levels in plasma of PV patients were significantly higher than those in normal controls(Ctrl)(P 0.01). Statistical analysis showed that there was no correlation between sCD147 expression level and PASI score(r =0.123, P =0.298). There was significant difference of sCD147 expression levels in different subtypes of psoriasis patients(PV PP PsA PE)(P 0.001). 【Conclusion】The expression levels of sCD147 is significantly increased in psoriasis patients. There is statistical significance of sCD147 expression levels in four subtypes of psoriasis. Thus, sCD147 may become a new target for psoriasis drug treatment.
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Introduction: T-helper 1 (Th1), Th17 cells, and their related cytokines are implicated in psoriasis pathogenesis although the contribution of each group of cytokines in psoriasis activity has not been fully clarified. Objectives: To investigate whether Th17-related cytokines are associated with psoriasis activity. Methods: The serum levels of interleukin (IL)-1β, 6, 8, 17Α, 22, 23, and tumor necrosis factor-α (TNFα) were measured with flow cytometry in 35 patients with plaque psoriasis (21 with stable and 14 with active disease) and in 20 healthy controls. Results: Interleukin-6, 8, 17A, 22, 23, and TNFα were significantly elevated in psoriasis patients compared with controls. In the sensitivity analyses, patients with active disease showed significantly increased levels of IL-17A, IL-23, and IL-22 as compared to the group of patients with stable psoriasis. Conclusions: Our study highlights a possible crucial role of IL-17A, IL-22, and IL-23 in the activity of psoriasis and the early stages of the disease.
Pathogenesis
Interleukin-23
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This chapter contains sections titled: Introduction History of psoriasis Who gets psoriasis? Biology of psoriasis Comorbidities associated with psoriasis Clinical variants of psoriasis Physical symptoms that accompany psoriasis Trigger factors in psoriasis Treatments for psoriasis Measuring quality of life Conclusion References
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Psoriasis treatment using psorinum autonosode is discussed. 50 years old male has been suffering from psoriasis for over three years with multiple psoriasis patches on his hands and feet. Psorinum autonosode was prepared from psoriasis scales using Korsakov’s method and taken twice a day. In about a month of taking the autonosode, the psoriasis patches disappeared completely and have not come back for over two years.
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