Research

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15 pages, 1194 KiB

Open AccessArticle

The Prostacyclin Analogue Iloprost Modulates CXCL10 in Systemic Sclerosis

by Tania Colasanti, Katia Stefanantoni, Cristina Fantini, Clarissa Corinaldesi, Massimiliano Vasile, Francesco Marampon, Luigi Di Luigi, Cristina Antinozzi, Paolo Sgrò, Andrea Lenzi, Valeria Riccieri and Clara Crescioli

Int. J. Mol. Sci. 2022, 23(17), 10150; https://doi.org/10.3390/ijms231710150 - 05 Sep 2022

Cited by 4 | Viewed by 2162

Abstract

The prostacyclin analogue iloprost is used to treat vascular alterations and digital ulcers, the early derangements manifesting in systemic sclerosis (SSc), an autoimmune disease leading to skin and organ fibrosis. Bioindicator(s) of SSc onset and progress are still lacking and the therapeutic approach [...] Read more.

The prostacyclin analogue iloprost is used to treat vascular alterations and digital ulcers, the early derangements manifesting in systemic sclerosis (SSc), an autoimmune disease leading to skin and organ fibrosis. Bioindicator(s) of SSc onset and progress are still lacking and the therapeutic approach remains a challenge. The T helper 1 (Th1) chemokine interferon (IFN)γ-induced protein 10 (IP-10/CXCL10) associates with disease progression and worse prognosis. Endothelial cells and fibroblasts, under Th1-dominance, release CXCL10, further enhancing SSc’s detrimental status. We analyzed the effect of iloprost on CXCL10 in endothelial cells, dermal fibroblasts, and in the serum of SSc patients. Human endothelial cells and dermal fibroblasts activated with IFNγ/Tumor Necrosis Factor (TNF)α, with/without iloprost, were investigated for CXCL10 secretion/expression and for intracellular signaling cascade underlying chemokine release (Signal Transducer and Activator of Transcription 1, STAT1; Nuclear Factor kappa-light-chain-enhancer of activated B cells, NF-kB; c-Jun NH₂-terminal kinase, JNK: Phosphatidyl-Inositol 3-kinase (PI3K)/protein kinase B, AKT; Extracellular signal-Regulated Kinase 1/2, ERK1/2). CXCL10 was quantified in sera from 25 patients taking iloprost, satisfying the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2013 classification criteria for SSc, and in sera from 20 SSc sex/age-matched subjects without therapy, previously collected. In human endothelial cells and fibroblasts, iloprost targeted CXCL10, almost preventing IFNγ/TNFα-dependent cascade activation in endothelial cells. In SSc subjects taking iloprost, serum CXCL10 was lower. These in vitro and in vivo data suggest a potential role of iloprost to limit CXCL10 at local vascular/dermal and systemic levels in SSc and warrant further translational research aimed to ameliorate SSc understanding/management. Full article

(This article belongs to the Special Issue Interconnecting Cytokine-Associated Molecular Pathways and Pathogenesis of Inflammatory Skin Diseases)

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19 pages, 1244 KiB

Open AccessArticle

Profiling Blood Serum Extracellular Vesicles in Plaque Psoriasis and Psoriatic Arthritis Patients Reveals Potential Disease Biomarkers

by Freddy Lättekivi, Irina Guljavina, Getnet Midekessa, Janeli Viil, Paul R. Heath, Rikke Bæk, Malene Møller Jørgensen, Aneta Andronowska, Kulli Kingo and Alireza Fazeli

Int. J. Mol. Sci. 2022, 23(7), 4005; https://doi.org/10.3390/ijms23074005 - 04 Apr 2022

Cited by 5 | Viewed by 3167

Abstract

Psoriasis vulgaris (PsV) and psoriatic arthritis (PsA) are inflammatory diseases with unresolved pathophysiological aspects. Extracellular vesicles (EVs) play an important role in intercellular communication. We compared the miRNA contents and surface proteome of the EVs in the blood serum of PsV and PsA [...] Read more.

Psoriasis vulgaris (PsV) and psoriatic arthritis (PsA) are inflammatory diseases with unresolved pathophysiological aspects. Extracellular vesicles (EVs) play an important role in intercellular communication. We compared the miRNA contents and surface proteome of the EVs in the blood serum of PsV and PsA patients to healthy controls. Size-exclusion chromatography was used to isolate EVs from the blood serum of 12 PsV patients, 12 PsA patients and 12 healthy control subjects. EV samples were characterized and RNA sequencing was used to identify differentially enriched EV-bound miRNAs. We found 212 differentially enriched EV-bound miRNAs present in both PsV and PsA groups—a total of 13 miRNAs at FDR ≤ 0.05. The predicted target genes of these miRNAs were significantly related to lesser known but potentially disease-relevant pathways. The EV array revealed that PsV patient EV samples were significantly enriched with CD9 EV-marker compared to controls. Analysis of EV-bound miRNAs suggests that signaling via EVs in the blood serum could play a role in the pathophysiological processes of PsV and PsA. EVs may be able to fill the void in clinically applicable diagnostic and prognostic biomarkers for PsV and PsA. Full article

(This article belongs to the Special Issue Interconnecting Cytokine-Associated Molecular Pathways and Pathogenesis of Inflammatory Skin Diseases)

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12 pages, 2488 KiB

Open AccessArticle

Rosmarinic Acid, as an NHE1 Activator, Decreases Skin Surface pH and Improves the Skin Barrier Function

by Seung-Won Jung, Gi Hyun Park, Eunjung Kim, Kang Min Yoo, Hea Won Kim, Jin Soo Lee, Min Youl Chang, Kyong-Oh Shin, Kyungho Park and Eung Ho Choi

Int. J. Mol. Sci. 2022, 23(7), 3910; https://doi.org/10.3390/ijms23073910 - 31 Mar 2022

Cited by 4 | Viewed by 2164

Abstract

Stratum corneum (SC) pH regulates skin barrier functions and elevated SC pH is an important factor in various inflammatory skin diseases. Acidic topical formulas have emerged as treatments for impaired skin barriers. Sodium proton exchanger 1 (NHE1) is an important factor in SC [...] Read more.

Stratum corneum (SC) pH regulates skin barrier functions and elevated SC pH is an important factor in various inflammatory skin diseases. Acidic topical formulas have emerged as treatments for impaired skin barriers. Sodium proton exchanger 1 (NHE1) is an important factor in SC acidification. We investigated whether topical applications containing an NHE1 activator could improve skin barrier functions. We screened plant extracts to identify NHE1 activators in vitro and found Melissa officinalis leaf extract. Rosmarinic acid, a component of Melissa officinalis leaf extract, significantly increased NHE1 mRNA expression levels and NHE1 production. Immunofluorescence staining of NHE1 in 3D-cultured skin revealed greater upregulation of NHE1 expression by NHE1 activator cream, compared to vehicle cream. Epidermal lipid analysis revealed that the ceramide level was significantly higher upon application of the NHE1 activator cream on 3D-cultured skin, compared to application of a vehicle cream. In a clinical study of 50–60-year-old adult females (n = 21), application of the NHE1 activator-containing cream significantly improved skin barrier functions by reducing skin surface pH and transepidermal water loss and increasing skin hydration, compared to patients who applied vehicle cream and those receiving no treatment. Thus, creams containing NHE1 activators, such as rosmarinic acid, could help maintain or recover skin barrier functions. Full article

(This article belongs to the Special Issue Interconnecting Cytokine-Associated Molecular Pathways and Pathogenesis of Inflammatory Skin Diseases)

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15 pages, 3481 KiB

Open AccessArticle

IL-17 Pathway Members as Potential Biomarkers of Effective Systemic Treatment and Cardiovascular Disease in Patients with Moderate-to-Severe Psoriasis

by Xing Wang, Hannah Kaiser, Amanda Kvist-Hansen, Benjamin D. McCauley, Lone Skov, Peter Riis Hansen and Christine Becker

Int. J. Mol. Sci. 2022, 23(1), 555; https://doi.org/10.3390/ijms23010555 - 05 Jan 2022

Cited by 13 | Viewed by 2935

Abstract

Psoriasis is a chronic inflammatory condition associated with atherosclerotic cardiovascular disease (CVD). Systemic anti-psoriatic treatments mainly include methotrexate and biological therapies targeting TNF, IL-12/23 and IL-17A. We profiled plasma proteins from patients with moderate-to-severe psoriasis to explore potential biomarkers of effective systemic treatment [...] Read more.

Psoriasis is a chronic inflammatory condition associated with atherosclerotic cardiovascular disease (CVD). Systemic anti-psoriatic treatments mainly include methotrexate and biological therapies targeting TNF, IL-12/23 and IL-17A. We profiled plasma proteins from patients with moderate-to-severe psoriasis to explore potential biomarkers of effective systemic treatment and their relationship to CVD. We found that systemically well-treated patients (PASI < 3.0, n = 36) had lower circulating levels of IL-17 pathway proteins compared to untreated patients (PASI > 10, n = 23). Notably, IL-17C and PI3 were decreased with all four examined systemic treatment types. Furthermore, in patients without CVD, we observed strong correlations among IL-17C/PI3/PASI (r ≥ 0.82, p ≤ 1.5 × 10⁻¹²) pairs or between IL-17A/PASI (r = 0.72, p = 9.3 × 10⁻⁸). In patients with CVD, the IL-17A/PASI correlation was abolished (r = 0.2, p = 0.24) and the other correlations were decreased, e.g., IL-17C/PI3 (r = 0.61, p = 4.5 × 10⁻⁵). Patients with moderate-to-severe psoriasis and CVD had lower levels of IL-17A compared to those without CVD (normalized protein expression [NPX] 2.02 vs. 2.55, p = 0.013), and lower IL-17A levels (NPX < 2.3) were associated with higher incidence of CVD (OR = 24.5, p = 0.0028, 95% CI 2.1–1425.1). As a result, in patients with moderate-to-severe psoriasis, we propose circulating IL-17C and PI3 as potential biomarkers of effective systemic anti-psoriatic treatment, and IL-17A as potential marker of CVD. Full article

(This article belongs to the Special Issue Interconnecting Cytokine-Associated Molecular Pathways and Pathogenesis of Inflammatory Skin Diseases)

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11 pages, 2948 KiB

Open AccessArticle

Phosphodiesterase-4 Inhibition Reduces Cutaneous Inflammation and IL-1β Expression in a Psoriasiform Mouse Model but Does Not Inhibit Inflammasome Activation

by Barbara Meier-Schiesser, Mark Mellett, Marigdalia K. Ramirez-Fort, Julia-Tatjana Maul, Annika Klug, Nicola Winkelbeiner, Gabriele Fenini, Peter Schafer, Emmanuel Contassot and Lars E. French

Int. J. Mol. Sci. 2021, 22(23), 12878; https://doi.org/10.3390/ijms222312878 - 28 Nov 2021

Cited by 2 | Viewed by 2390

Abstract

Apremilast (Otezla^®) is an oral small molecule phosphodiesterase 4 (PDE4) inhibitor approved for the treatment of psoriasis, psoriatic arthritis, and oral ulcers associated with Behçet’s disease. While PDE4 inhibition overall is mechanistically understood, the effect of apremilast on the innate immune [...] Read more.

Apremilast (Otezla^®) is an oral small molecule phosphodiesterase 4 (PDE4) inhibitor approved for the treatment of psoriasis, psoriatic arthritis, and oral ulcers associated with Behçet’s disease. While PDE4 inhibition overall is mechanistically understood, the effect of apremilast on the innate immune response, particularly inflammasome activation, remains unknown. Here, we assessed the effect of apremilast in a psoriasis mouse model and primary human cells. Psoriatic lesion development in vivo was studied in K5.Stat3C transgenic mice treated with apremilast for 2 weeks, resulting in a moderate (2 mg/kg/day) to significant (6 mg/kg/day) resolution of inflamed plaques after 2-week treatment. Concomitantly, epidermal thickness dramatically decreased, the cutaneous immune cell infiltrate was reduced, and proinflammatory cytokines were significantly downregulated. Additionally, apremilast significantly inhibited lipopolysaccharide- or anti-CD3-induced expression of proinflammatory cytokines in peripheral mononuclear cells (PBMCs). Notably, inflammasome activation and secretion of IL-1β were not inhibited by apremilast in PBMCs and in human primary keratinocytes. Collectively, apremilast effectively alleviated the psoriatic phenotype of K5.Stat3 transgenic mice, further substantiating PDE4 inhibitor-efficiency in targeting key clinical, histopathological and inflammatory features of psoriasis. Despite lacking direct effect on inflammasome activation, reduced priming of inflammasome components upon apremilast treatment reflected the indirect benefit of PDE4 inhibition in reducing inflammation. Full article

(This article belongs to the Special Issue Interconnecting Cytokine-Associated Molecular Pathways and Pathogenesis of Inflammatory Skin Diseases)

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12 pages, 2719 KiB

Open AccessArticle

Isoprocurcumenol Supports Keratinocyte Growth and Survival through Epidermal Growth Factor Receptor Activation

by Paul Kwangho Kwon, Sung Wook Kim, Ranjit De, Sung Woo Jeong and Kyong-Tai Kim

Int. J. Mol. Sci. 2021, 22(22), 12579; https://doi.org/10.3390/ijms222212579 - 22 Nov 2021

Cited by 6 | Viewed by 1900

Abstract

Although proliferation of keratinocytes, a major type of skin cells, is a key factor in maintaining the function of skin, their ability to proliferate tends to diminish with age. To solve such a problem, researchers in medical and skin cosmetic fields have tried [...] Read more.

Although proliferation of keratinocytes, a major type of skin cells, is a key factor in maintaining the function of skin, their ability to proliferate tends to diminish with age. To solve such a problem, researchers in medical and skin cosmetic fields have tried to utilize epidermal growth factor (EGF), but achieved limited success. Therefore, a small natural compound that can mimic the activity of EGF is highly desired in both medical and cosmetic fields. Here, using the modified biosensor system, we observed that natural small-compound isoprocurcumenol, which is a terpenoid molecule derived from turmeric, can activate EGFR signaling. It increased the phosphorylation of ERK and AKT, and upregulated the expression of genes related to cell growth and proliferation, such as c-myc, c-jun, c-fos, and egr-1. In addition, isoprocurcumenol induced the proliferation of keratinocytes in both physical and UVB-induced cellular damage, indicative of its function in skin regeneration. These findings reveal that EGF-like isoprocurcumenol promotes the proliferation of keratinocytes and further suggest its potential as an ingredient for medical and cosmetics use. Full article

(This article belongs to the Special Issue Interconnecting Cytokine-Associated Molecular Pathways and Pathogenesis of Inflammatory Skin Diseases)

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15 pages, 4723 KiB

Open AccessArticle

Glycerol Improves Skin Lesion Development in the Imiquimod Mouse Model of Psoriasis: Experimental Confirmation of Anecdotal Reports from Patients with Psoriasis

by Vivek Choudhary, Ismail Kaddour-Djebbar, Victoria E. Custer, Rawipan Uaratanawong, Xunsheng Chen, Elyssa Cohen, Rong Yang, Etsubdenk Ajebo, Sarah Hossack and Wendy B. Bollag

Int. J. Mol. Sci. 2021, 22(16), 8749; https://doi.org/10.3390/ijms22168749 - 15 Aug 2021

Cited by 11 | Viewed by 5369

Abstract

Glycerol is used in many skin care products because it improves skin function. Anecdotal reports by patients on the National Psoriasis Foundation website also suggest that glycerol may be helpful for the treatment of psoriasis, although to date no experimental data confirm this [...] Read more.

Glycerol is used in many skin care products because it improves skin function. Anecdotal reports by patients on the National Psoriasis Foundation website also suggest that glycerol may be helpful for the treatment of psoriasis, although to date no experimental data confirm this idea. Glycerol entry into epidermal keratinocytes is facilitated by aquaglyceroporins like aquaporin-3 (AQP3), and its conversion to phosphatidylglycerol, a lipid messenger that promotes keratinocyte differentiation, requires the lipid-metabolizing enzyme phospholipase-D2 (PLD2). To evaluate whether glycerol inhibits inflammation and psoriasiform lesion development in the imiquimod (IMQ)-induced mouse model of psoriasis, glycerol’s effect on psoriasiform skin lesions was determined in IMQ-treated wild-type and PLD2 knockout mice, with glycerol provided either in drinking water or applied topically. Psoriasis area and severity index, ear thickness and ear biopsy weight, epidermal thickness, and inflammatory markers were quantified. Topical and oral glycerol ameliorated psoriasiform lesion development in wild-type mice. Topical glycerol appeared to act as an emollient to induce beneficial effects, since even in PLD2 knockout mice topical glycerol application improved skin lesions. In contrast, the beneficial effects of oral glycerol required PLD2, with no improvement in psoriasiform lesions observed in PLD2 knockout mice. Our findings suggest that the ability of oral glycerol to improve psoriasiform lesions requires its PLD2-mediated conversion to phosphatidylglycerol, consistent with our previous report that phosphatidylglycerol itself improves psoriasiform lesions in this model. Our data also support anecdotal evidence that glycerol can ameliorate psoriasis symptoms and therefore might be a useful therapy alone or in conjunction with other treatments. Full article

(This article belongs to the Special Issue Interconnecting Cytokine-Associated Molecular Pathways and Pathogenesis of Inflammatory Skin Diseases)

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23 pages, 26552 KiB

Open AccessArticle

Enhanced NAMPT-Mediated NAD Salvage Pathway Contributes to Psoriasis Pathogenesis by Amplifying Epithelial Auto-Inflammatory Circuits

by Laura Mercurio, Martina Morelli, Claudia Scarponi, Giovanni Luca Scaglione, Sabatino Pallotta, Daniele Avitabile, Cristina Albanesi and Stefania Madonna

Int. J. Mol. Sci. 2021, 22(13), 6860; https://doi.org/10.3390/ijms22136860 - 25 Jun 2021

Cited by 6 | Viewed by 3644

Abstract

Dysregulated cross-talk between immune cells and epithelial compartments is responsible for the onset and amplification of pathogenic auto-inflammatory circuits occurring in psoriasis. NAMPT-mediated NAD salvage pathway has been recently described as an immunometabolic route having inflammatory function in several disorders, including arthritis and [...] Read more.

Dysregulated cross-talk between immune cells and epithelial compartments is responsible for the onset and amplification of pathogenic auto-inflammatory circuits occurring in psoriasis. NAMPT-mediated NAD salvage pathway has been recently described as an immunometabolic route having inflammatory function in several disorders, including arthritis and inflammatory bowel diseases. To date, the role of NAD salvage pathway has not been explored in the skin of patients affected by psoriasis. Here, we show that NAD content is enhanced in lesional skin of psoriatic patients and is associated to high NAMPT transcriptional levels. The latter are drastically reduced in psoriatic skin following treatment with the anti-IL-17A biologics secukinumab. We provide evidence that NAMPT-mediated NAD⁺ metabolism fuels the immune responses executed by resident skin cells in psoriatic skin. In particular, intracellular NAMPT, strongly induced by Th1/Th17-cytokines, acts on keratinocytes by inducing hyper-proliferation and impairing their terminal differentiation. Furthermore, NAMPT-mediated NAD⁺ boosting synergizes with psoriasis-related cytokines in the upregulation of inflammatory chemokines important for neutrophil and Th1/Th17 cell recruitment. In addition, extracellular NAMPT, abundantly released by keratinocytes and dermal fibroblasts, acts in a paracrine manner on endothelial cells by inducing their proliferation and migration, as well as the expression of ICAM-1 membrane molecule and chemokines important for leukocyte recruitment into inflamed skin. In conclusion, our results showed that NAMPT-mediated NAD salvage pathway contributes to psoriasis pathogenic processes by amplifying epithelial auto-inflammatory responses in psoriasis. Full article

(This article belongs to the Special Issue Interconnecting Cytokine-Associated Molecular Pathways and Pathogenesis of Inflammatory Skin Diseases)

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Review

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31 pages, 6693 KiB

Open AccessReview

Chronic Inflammation in Non-Healing Skin Wounds and Promising Natural Bioactive Compounds Treatment

by Priscila Schilrreff and Ulrike Alexiev

Int. J. Mol. Sci. 2022, 23(9), 4928; https://doi.org/10.3390/ijms23094928 - 28 Apr 2022

Cited by 53 | Viewed by 10925

Abstract

Chronic inflammation is one of the hallmarks of chronic wounds and is tightly coupled to immune regulation. The dysregulation of the immune system leads to continuing inflammation and impaired wound healing and, subsequently, to chronic skin wounds. In this review, we discuss the [...] Read more.

Chronic inflammation is one of the hallmarks of chronic wounds and is tightly coupled to immune regulation. The dysregulation of the immune system leads to continuing inflammation and impaired wound healing and, subsequently, to chronic skin wounds. In this review, we discuss the role of the immune system, the involvement of inflammatory mediators and reactive oxygen species, the complication of bacterial infections in chronic wound healing, and the still-underexplored potential of natural bioactive compounds in wound treatment. We focus on natural compounds with antioxidant, anti-inflammatory, and antibacterial activities and their mechanisms of action, as well as on recent wound treatments and therapeutic advancements capitalizing on nanotechnology or new biomaterial platforms. Full article

(This article belongs to the Special Issue Interconnecting Cytokine-Associated Molecular Pathways and Pathogenesis of Inflammatory Skin Diseases)

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17 pages, 1193 KiB

Open AccessReview

Multiple Roles for Cytokines in Atopic Dermatitis: From Pathogenic Mediators to Endotype-Specific Biomarkers to Therapeutic Targets

by Luca Fania, Gaia Moretta, Flaminia Antonelli, Enrico Scala, Damiano Abeni, Cristina Albanesi and Stefania Madonna

Int. J. Mol. Sci. 2022, 23(5), 2684; https://doi.org/10.3390/ijms23052684 - 28 Feb 2022

Cited by 25 | Viewed by 6799

Abstract

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, which generally presents with intense itching and recurrent eczematous lesions. AD affects up to 20% of children and 10% of adults in high-income countries. The prevalence and incidence of AD [...] Read more.

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, which generally presents with intense itching and recurrent eczematous lesions. AD affects up to 20% of children and 10% of adults in high-income countries. The prevalence and incidence of AD have increased in recent years. The onset of AD mostly occurs in childhood, although in some cases AD may persist in adult life or even manifest in middle age (adult-onset AD). AD pathophysiology is made of a complex net, in which genetic background, skin barrier dysfunction, innate and adaptive immune responses, as well as itch contribute to disease development, progression, and chronicization. One of the most important features of AD is skin dehydration, which is mainly caused by filaggrin mutations that determine trans-epidermal water loss, pH alterations, and antigen penetration. In accordance with the “outside-inside” theory of AD pathogenesis, in a context of an altered epidermal barrier, antigens encounter epidermal antigen presentation cells (APCs), such as epidermal Langerhans cells and inflammatory epidermal dendritic cells, leading to their maturation and Th-2 cell-mediated inflammation. APCs also bear trimeric high-affinity receptors for immunoglobulin E (IgE), which induce IgE-mediated sensitizations as part of pathogenic mechanisms leading to AD. In this review, we discuss the role of cytokines in the pathogenesis of AD, considering patients with various clinical AD phenotypes. Moreover, we describe the cytokine patterns in patients with AD at different phases of the disease evolution, as well as in relation to different phenotypes/endotypes, including age, race, and intrinsic/extrinsic subtypes. We also discuss the outcomes of current biologics for AD, which corroborate the presence of multiple cytokine axes involved in the background of AD. A deep insight into the correlation between cytokine patterns and the related clinical forms of AD is a crucial step towards increasingly personalized, and therefore more efficient therapy. Full article

(This article belongs to the Special Issue Interconnecting Cytokine-Associated Molecular Pathways and Pathogenesis of Inflammatory Skin Diseases)

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23 pages, 622 KiB

Open AccessReview

The Cytokine Mediated Molecular Pathophysiology of Psoriasis and Its Clinical Implications

by Rohan Singh, Sindhuja Koppu, Patrick O. Perche and Steven R. Feldman

Int. J. Mol. Sci. 2021, 22(23), 12793; https://doi.org/10.3390/ijms222312793 - 26 Nov 2021

Cited by 48 | Viewed by 7376

Abstract

Psoriasis is the result of uncontrolled keratinocyte proliferation, and its pathogenesis involves the dysregulation of the immune system. The interplay among cytokines released by dendritic, T_h1, T_h2, and T_h17 cells leads to the phenotypical manifestations seen in [...] Read more.

Psoriasis is the result of uncontrolled keratinocyte proliferation, and its pathogenesis involves the dysregulation of the immune system. The interplay among cytokines released by dendritic, T_h1, T_h2, and T_h17 cells leads to the phenotypical manifestations seen in psoriasis. Biological therapies target the cytokine-mediated pathogenesis of psoriasis and have improved patient quality of life. This review will describe the underlying molecular pathophysiology and biologics used to treat psoriasis. A review of the literature was conducted using the PubMed and Google Scholar repositories to investigate the molecular pathogenesis, clinical presentation, and current therapeutics in psoriasis. Plaque psoriasis’, the most prevalent subtype of psoriasis, pathogenesis primarily involves cytokines TNF-α, IL-17, and IL-23. Pustular psoriasis’, an uncommon variant, pathogenesis involves a mutation in IL-36RN. Currently, biological therapeutics targeted at TNF-α, IL-12/IL-23, IL-17, and IL-23/IL-39 are approved for the treatment of moderate to severe psoriasis. More studies need to be performed to elucidate the precise molecular pathology and assess efficacy between biological therapies for psoriasis. Psoriasis is a heterogenous, chronic, systemic inflammatory disease that presents in the skin with multiple types. Recognizing and understanding the underlying molecular pathways and biological therapeutics to treat psoriasis is important in treating this common disease. Full article

(This article belongs to the Special Issue Interconnecting Cytokine-Associated Molecular Pathways and Pathogenesis of Inflammatory Skin Diseases)

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16 pages, 662 KiB

Open AccessReview

The Role of Epigenetic Factors in Psoriasis

by Klaudia Dopytalska, Piotr Ciechanowicz, Kacper Wiszniewski, Elżbieta Szymańska and Irena Walecka

Int. J. Mol. Sci. 2021, 22(17), 9294; https://doi.org/10.3390/ijms22179294 - 27 Aug 2021

Cited by 53 | Viewed by 4573

Abstract

Psoriasis is a chronic, systemic, immune-mediated disease with an incidence of approximately 2%. The pathogenesis of the disease is complex and not yet fully understood. Genetic factors play a significant role in the pathogenesis of the disease. In predisposed individuals, multiple trigger factors [...] Read more.

Psoriasis is a chronic, systemic, immune-mediated disease with an incidence of approximately 2%. The pathogenesis of the disease is complex and not yet fully understood. Genetic factors play a significant role in the pathogenesis of the disease. In predisposed individuals, multiple trigger factors may contribute to disease onset and exacerbations of symptoms. Environmental factors (stress, infections, certain medications, nicotinism, alcohol, obesity) play a significant role in the pathogenesis of psoriasis. In addition, epigenetic mechanisms are considered result in modulation of individual gene expression and an increased likelihood of the disease. Studies highlight the significant role of epigenetic factors in the etiology and pathogenesis of psoriasis. Epigenetic mechanisms in psoriasis include DNA methylation, histone modifications and non-coding RNAs. Epigenetic mechanisms induce gene expression changes under the influence of chemical modifications of DNA and histones, which alter chromatin structure and activate transcription factors of selected genes, thus leading to translation of new mRNA without affecting the DNA sequence. Epigenetic factors can regulate gene expression at the transcriptional (via histone modification, DNA methylation) and posttranscriptional levels (via microRNAs and long non-coding RNAs). This study aims to present and discuss the different epigenetic mechanisms in psoriasis based on a review of the available literature. Full article

(This article belongs to the Special Issue Interconnecting Cytokine-Associated Molecular Pathways and Pathogenesis of Inflammatory Skin Diseases)

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