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Open AccessArticle

Systemic Inflammation, Oxidative Damage to Nucleic Acids, and Metabolic Syndrome in the Pathogenesis of Psoriasis

by Lenka Borska, Jan Kremlacek, Ctirad Andrys, Jan Krejsek, Kvetoslava Hamakova, Pavel Borsky, Vladimir Palicka, Vit Rehacek, Andrea Malkova and Zdenek Fiala

Int. J. Mol. Sci. 2017, 18(11), 2238; https://doi.org/10.3390/ijms18112238 - 25 Oct 2017

Cited by 40 | Viewed by 8575

Abstract

In the pathogenesis of psoriasis, systemic inflammation and oxidative stress play mutual roles interrelated with metabolic syndrome (MetS). This study aims to map the selected markers of inflammation (C-reactive protein (CRP)), oxidative damage to nucleic acids (DNA/RNA damage; 8-hydroxy-2′-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), and [...] Read more.

In the pathogenesis of psoriasis, systemic inflammation and oxidative stress play mutual roles interrelated with metabolic syndrome (MetS). This study aims to map the selected markers of inflammation (C-reactive protein (CRP)), oxidative damage to nucleic acids (DNA/RNA damage; 8-hydroxy-2′-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), and the parameters of MetS (waist circumference, fasting glucose, triglycerides, high-density lipoprotein (HDL) cholesterol, diastolic and systolic blood pressure) in a group of 37 patients with psoriasis (62% of MetS) and in 43 healthy controls (42% of MetS). Levels of CRP, DNA/RNA damage, fasting glucose, and triglycerides were significantly elevated in patients. MetS in conjunction with psoriasis was associated with high levels of CRP, significantly higher than in control subjects without MetS. Patients with MetS exhibited further DNA/RNA damage, which was significantly higher in comparison with the control group. Our study supports the independent role of psoriasis and MetS in the increase of CRP and DNA/RNA damage. The psoriasis contributes to an increase in the levels of both effects more significantly than MetS. The psoriasis also diminished the relationship between CRP and oxidative damage to nucleic acids existent in controls. Full article

(This article belongs to the Special Issue Psoriasis)

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31 pages, 3687 KiB

Open AccessReview

Scanning the Immunopathogenesis of Psoriasis

by Andrea Chiricozzi, Paolo Romanelli, Elisabetta Volpe, Giovanna Borsellino and Marco Romanelli

Int. J. Mol. Sci. 2018, 19(1), 179; https://doi.org/10.3390/ijms19010179 - 08 Jan 2018

Cited by 215 | Viewed by 13948

Abstract

Psoriasis is a chronic inflammatory skin disease, the immunologic model of which has been profoundly revised following recent advances in the understanding of its pathophysiology. In the current model, a crosstalk between keratinocytes, neutrophils, mast cells, T cells, and dendritic cells is thought [...] Read more.

Psoriasis is a chronic inflammatory skin disease, the immunologic model of which has been profoundly revised following recent advances in the understanding of its pathophysiology. In the current model, a crosstalk between keratinocytes, neutrophils, mast cells, T cells, and dendritic cells is thought to create inflammatory and pro-proliferative circuits mediated by chemokines and cytokines. Various triggers, including recently identified autoantigens, Toll-like receptor agonists, chemerin, and thymic stromal lymphopoietin may activate the pathogenic cascade resulting in enhanced production of pro-inflammatory and proliferation-inducing mediators such as interleukin (IL)-17, tumor necrosis factor (TNF)-α, IL-23, IL-22, interferon (IFN)-α, and IFN-γ by immune cells. Among these key cytokines lie therapeutic targets for currently approved antipsoriatic therapies. This review aims to provide a comprehensive overview on the immune-mediated mechanisms characterizing the current pathogenic model of psoriasis. Full article

(This article belongs to the Special Issue Psoriasis)

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292 KiB

Open AccessReview

Cardiometabolic Comorbidities in Psoriasis and Psoriatic Arthritis

by Lluís Puig

Int. J. Mol. Sci. 2018, 19(1), 58; https://doi.org/10.3390/ijms19010058 - 25 Dec 2017

Cited by 87 | Viewed by 7093

Abstract

There is solid epidemiologic evidence linking psoriasis and psoriatic arthritis (PsA) to cardiovascular risk factors and an increased risk of developing cardiovascular disease. Chronic inflammation, with shared pathways and cytokines common to metabolic syndrome, atherosclerosis and psoriasis, might provide the basis for the [...] Read more.

There is solid epidemiologic evidence linking psoriasis and psoriatic arthritis (PsA) to cardiovascular risk factors and an increased risk of developing cardiovascular disease. Chronic inflammation, with shared pathways and cytokines common to metabolic syndrome, atherosclerosis and psoriasis, might provide the basis for the cardiovascular and metabolic comorbidities of psoriasis and PsA. The purpose of this manuscript is to review recent evidence about the epidemiology and underlying mechanisms of cardiovascular risk factors and cardiovascular disease in patients with psoriasis and/or PsA; the use of analytical determinations, physiologic measures and imaging techniques as surrogate biomarkers of atherosclerosis, endothelial dysfunction and cardiovascular disease in these patients; and the epidemiological and clinical data, including results of clinical trials, supporting a cardioprotective role of anti-inflammatory and disease-modifying treatment in psoriasis and PsA. Full article

(This article belongs to the Special Issue Psoriasis)

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Open AccessReview

The Immunogenetics of Psoriasis and Implications for Drug Repositioning

by Xuan Xu and Hong-Yu Zhang

Int. J. Mol. Sci. 2017, 18(12), 2650; https://doi.org/10.3390/ijms18122650 - 08 Dec 2017

Cited by 20 | Viewed by 4490

Abstract

Psoriasis is a genetically-regulated, T lymphocyte-mediated autoimmune skin disease that causes systemic damage, seriously affecting patient quality of life and survival. Psoriasis treatments, which aim to control the disease’s development, are greatly limited because its etiology and pathogenesis have not yet been fully [...] Read more.

Psoriasis is a genetically-regulated, T lymphocyte-mediated autoimmune skin disease that causes systemic damage, seriously affecting patient quality of life and survival. Psoriasis treatments, which aim to control the disease’s development, are greatly limited because its etiology and pathogenesis have not yet been fully elucidated. A large number of studies have demonstrated that immunogenetic elements are the most important factors responsible for psoriasis susceptibility. This paper delineates the immunogenetic mechanisms of psoriasis and provides useful information with regards to performing drug repositioning for the treatment of psoriasis. Full article

(This article belongs to the Special Issue Psoriasis)

189 KiB

Open AccessReview

The Genetic Basis of Psoriasis

by Francesca Capon

Int. J. Mol. Sci. 2017, 18(12), 2526; https://doi.org/10.3390/ijms18122526 - 25 Nov 2017

Cited by 138 | Viewed by 12280

Abstract

Psoriasis is widely regarded as a multifactorial condition which is caused by the interaction between inherited susceptibility alleles and environmental triggers. In the last decade, technological advances have enabled substantial progress in the understanding of disease genetics. Genome-wide association studies have identified more [...] Read more.

Psoriasis is widely regarded as a multifactorial condition which is caused by the interaction between inherited susceptibility alleles and environmental triggers. In the last decade, technological advances have enabled substantial progress in the understanding of disease genetics. Genome-wide association studies have identified more than 60 disease susceptibility regions, highlighting the pathogenic involvement of genes related to Th17 cell activation. This pathway has now been targeted by a new generation of biologics that have shown great efficacy in clinical trials. At the same time, the study of rare variants of psoriasis has identified interleukin (IL)-36 cytokines as important amplifiers of Th17 signaling and promising targets for therapeutic intervention. Here, we review these exciting discoveries, which highlight the translational potential of genetic studies. Full article

(This article belongs to the Special Issue Psoriasis)

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Open AccessReview

Models in the Research Process of Psoriasis

by Katarzyna Bocheńska, Elwira Smolińska, Marta Moskot, Joanna Jakóbkiewicz-Banecka and Magdalena Gabig-Cimińska

Int. J. Mol. Sci. 2017, 18(12), 2514; https://doi.org/10.3390/ijms18122514 - 24 Nov 2017

Cited by 85 | Viewed by 12956

Abstract

Psoriasis is an ancient, universal chronic skin disease with a significant geographical variability, with the lowest incidence rate at the equator, increasing towards the poles. Insights into the mechanisms responsible for psoriasis have generated an increasing number of druggable targets and molecular drugs. [...] Read more.

Psoriasis is an ancient, universal chronic skin disease with a significant geographical variability, with the lowest incidence rate at the equator, increasing towards the poles. Insights into the mechanisms responsible for psoriasis have generated an increasing number of druggable targets and molecular drugs. The development of relevant in vitro and in vivo models of psoriasis is now a priority and an important step towards its cure. In this review, we summarize the current cellular and animal systems suited to the study of psoriasis. We discuss the strengths and limitations of the various models and the lessons learned. We conclude that, so far, there is no one model that can meet all of the research needs. Therefore, the choice model system will depend on the questions being addressed. Full article

(This article belongs to the Special Issue Psoriasis)

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812 KiB

Open AccessReview

Advanced Glycation End Products in the Pathogenesis of Psoriasis

by Anastasia Papagrigoraki, Martina Maurelli, Micol Del Giglio, Paolo Gisondi and Giampiero Girolomoni

Int. J. Mol. Sci. 2017, 18(11), 2471; https://doi.org/10.3390/ijms18112471 - 20 Nov 2017

Cited by 44 | Viewed by 9138

Abstract

Advanced glycation end products (AGEs) are extremely oxidant and biologically reactive compounds, which form through oxidation of sugars, lipids and amino acids to create aldehydes that bind covalently to proteins. AGEs formation and accumulation in human tissues is a physiological process during ageing [...] Read more.

Advanced glycation end products (AGEs) are extremely oxidant and biologically reactive compounds, which form through oxidation of sugars, lipids and amino acids to create aldehydes that bind covalently to proteins. AGEs formation and accumulation in human tissues is a physiological process during ageing but it is enhanced in case of persistent hyperglycemia, hyperlipidemia and oxidative or carbonyl stress, which are common in patients with moderate to severe psoriasis. Exogenous AGEs may derive from foods, UV irradiation and cigarette smoking. AGEs elicit biological functions by activating membrane receptors expressed on epithelial and inflammatory cell surface. AGEs amplify inflammatory response by favoring the release of cytokines and chemokines, the production of reactive oxygen species and the activation of metalloproteases. AGEs levels are increased in the skin and blood of patients with severe psoriasis independently of associated metabolic disorders. Intensified glycation of proteins in psoriasis skin might have a role in fueling cutaneous inflammation. In addition, AGEs released from psoriatic skin may increase metabolic and cardiovascular risk in patients with severe disease. Full article

(This article belongs to the Special Issue Psoriasis)

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Open AccessReview

Treatment Approaches to Moderate to Severe Psoriasis

by Paolo Gisondi, Micol Del Giglio and Giampiero Girolomoni

Int. J. Mol. Sci. 2017, 18(11), 2427; https://doi.org/10.3390/ijms18112427 - 16 Nov 2017

Cited by 92 | Viewed by 24114

Abstract

Psoriasis is a common disease, which has a considerable impact on patients and the health care system. Treatment approaches to the disease may be various because some issues are not definitely addressed. Moreover, the therapeutic paradigms are continuously changing because of the recent [...] Read more.

Psoriasis is a common disease, which has a considerable impact on patients and the health care system. Treatment approaches to the disease may be various because some issues are not definitely addressed. Moreover, the therapeutic paradigms are continuously changing because of the recent approval of new treatments for psoriasis such as interleukin (IL)-17 inhibitors and apremilast. In this review, the factors influencing psoriasis severity, the indications for systemic treatments, the overall parameters to be considered in the treatment choice, life style interventions, and the recommendations for the use, screening, and monitoring of systemic therapies available including acitretin, cyclosporine, methotrexate, apremilast, adalimumab, etanercept, infliximab, secukinumab, ixekizumab, and ustekinumab are discussed. Finally, treatment approaches in special patient populations including children, the elderly, pregnant women, patients with a history of neoplasm, and candidates for surgical procedures are reported. Full article

(This article belongs to the Special Issue Psoriasis)

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Old and New Biological Therapies for Psoriasis

by Kirsten Rønholt and Lars Iversen

Int. J. Mol. Sci. 2017, 18(11), 2297; https://doi.org/10.3390/ijms18112297 - 01 Nov 2017

Cited by 180 | Viewed by 18616

Abstract

Biological therapy became available for psoriasis with the introduction of alefacept at the beginning of this century. Up to then, systemic treatment options comprised small molecule drugs, targeting the immune system in a non-specific manner. The first biologics targeted T-cell activation and migration [...] Read more.

Biological therapy became available for psoriasis with the introduction of alefacept at the beginning of this century. Up to then, systemic treatment options comprised small molecule drugs, targeting the immune system in a non-specific manner. The first biologics targeted T-cell activation and migration and served as an alternative to small molecules. However, significant improvement in outcome was first accomplished with the introduction of tumor necrosis factor-α inhibitors that were already approved for other inflammatory disorders, including rheumatic diseases. Along with the progress in understanding psoriasis pathogenesis, highly targeted and effective therapies have since developed with the perspective not only to improve but to clear psoriasis. These accomplishments enable future achievement of advanced goals to individualize treatment best suited for each patient. Mechanistic studies with patients treated with the new highly targeted biologics may guide us towards these goals. This review offers an overview of biologics developed for psoriasis and illustrate a historical progress in the treatment of this common chronic inflammatory skin condition. Full article

(This article belongs to the Special Issue Psoriasis)

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Open AccessReview

Psoriasis and Cardiovascular Comorbidities: Focusing on Severe Vascular Events, Cardiovascular Risk Factors and Implications for Treatment

by Stephen Chu-Sung Hu and Cheng-Che E. Lan

Int. J. Mol. Sci. 2017, 18(10), 2211; https://doi.org/10.3390/ijms18102211 - 21 Oct 2017

Cited by 118 | Viewed by 11428

Abstract

Psoriasis is a common and chronic inflammatory disease of the skin. It may impair the physical and psychosocial function of patients and lead to decreased quality of life. Traditionally, psoriasis has been regarded as a disease affecting only the skin and joints. More [...] Read more.

Psoriasis is a common and chronic inflammatory disease of the skin. It may impair the physical and psychosocial function of patients and lead to decreased quality of life. Traditionally, psoriasis has been regarded as a disease affecting only the skin and joints. More recently, studies have shown that psoriasis is a systemic inflammatory disorder which can be associated with various comorbidities. In particular, psoriasis is associated with an increased risk of developing severe vascular events such as myocardial infarction and stroke. In addition, the prevalence rates of cardiovascular risk factors are increased, including hypertension, diabetes mellitus, dyslipidemia, obesity, and metabolic syndrome. Consequently, mortality rates have been found to be increased and life expectancy decreased in patients with psoriasis, as compared to the general population. Various studies have also shown that systemic treatments for psoriasis, including methotrexate and tumor necrosis factor-α inhibitors, may significantly decrease cardiovascular risk. Mechanistically, the presence of common inflammatory pathways, secretion of adipokines, insulin resistance, angiogenesis, oxidative stress, microparticles, and hypercoagulability may explain the association between psoriasis and cardiometabolic disorders. In this article, we review the evidence regarding the association between psoriasis and cardiovascular comorbidities, focusing on severe vascular events, cardiovascular risk factors and implications for treatment. Full article

(This article belongs to the Special Issue Psoriasis)

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Stem Cells as Potential Candidates for Psoriasis Cell-Replacement Therapy

by Agnieszka Owczarczyk-Saczonek, Magdalena Krajewska-Włodarczyk, Anna Kruszewska, Waldemar Placek, Wojciech Maksymowicz and Joanna Wojtkiewicz

Int. J. Mol. Sci. 2017, 18(10), 2182; https://doi.org/10.3390/ijms18102182 - 20 Oct 2017

Cited by 23 | Viewed by 7672

Abstract

Recent years have seen considerable progress in explaining the mechanisms of the pathogenesis of psoriasis, with a significant role played in it by the hyper-reactivity of Th1 and Th17 cells, Treg function disorder, as well as complex relationships between immune cells, keratinocytes, and [...] Read more.

Recent years have seen considerable progress in explaining the mechanisms of the pathogenesis of psoriasis, with a significant role played in it by the hyper-reactivity of Th1 and Th17 cells, Treg function disorder, as well as complex relationships between immune cells, keratinocytes, and vascular endothelium. The effect of stem cells in the epidermis and stem cells on T cells has been identified and the dysfunction of various types of stem cells may be a prime cause of dysregulation of the inflammatory response in psoriasis. However, exploring these mechanisms in detail could provide a chance to develop new therapeutic strategies. In this paper, the authors reviewed data on the role played by stem cells in the pathogenesis of psoriasis and initial attempts at using them in treatment. Full article

(This article belongs to the Special Issue Psoriasis)

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