Research

15 pages, 9434 KiB

Open AccessArticle

Dihydrochalcone Derivatives from Populus balsamifera L. Buds for the Treatment of Psoriasis

by Audrey Bélanger, Alexe Grenier, François Simard, Isabelle Gendreau, André Pichette, Jean Legault and Roxane Pouliot

Int. J. Mol. Sci. 2020, 21(1), 256; https://doi.org/10.3390/ijms21010256 - 30 Dec 2019

Cited by 22 | Viewed by 3491

Abstract

Psoriasis is a skin disorder characterized by epidermal hyperplasia, hyperkeratosis, and inflammation. The treatments currently available on the market only improve patients’ quality of life and are associated with undesirable side effects. Thus, research leading to the development of new, effective, and safer [...] Read more.

Psoriasis is a skin disorder characterized by epidermal hyperplasia, hyperkeratosis, and inflammation. The treatments currently available on the market only improve patients’ quality of life and are associated with undesirable side effects. Thus, research leading to the development of new, effective, and safer therapeutic agents is still relevant. Populus balsamifera L. buds were used traditionally by Native Americans to treat various skin pathologies such as eczema and psoriasis. In this study, the antipsoriatic activities of dihydrochalcone derivatives from Populus balsamifera L. buds, known as balsacones, were investigated. The experiments were performed in vitro using a psoriatic skin substitute model. Also, anti-inflammatory and antioxidant activities were investigated. The tested balsacones showed promising antipsoriatic properties by slowing down cell growth and by regulating the expression of involucrin, loricrin, and Ki67 better than methotrexate in psoriatic substitutes. All five tested compounds could be an effective topical treatment for psoriasis, with promising anti-inflammatory and antioxidant actions that may contribute to clinical improvement in patients with psoriasis. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Pathology of Psoriasis)

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23 pages, 4775 KiB

Open AccessArticle

Lysosome Alterations in the Human Epithelial Cell Line HaCaT and Skin Specimens: Relevance to Psoriasis

by Katarzyna Bocheńska, Marta Moskot, Marcelina Malinowska, Joanna Jakóbkiewicz-Banecka, Aneta Szczerkowska-Dobosz, Dorota Purzycka-Bohdan, Joanna Pleńkowska, Bartosz Słomiński and Magdalena Gabig-Cimińska

Int. J. Mol. Sci. 2019, 20(9), 2255; https://doi.org/10.3390/ijms20092255 - 07 May 2019

Cited by 12 | Viewed by 6129 | Correction

Abstract

Despite the constantly updated knowledge regarding the alterations occurring in the cells of patients with psoriasis, the status and the role of the lysosome, a control center of cell metabolism, remain to be elucidated. The architecture of the epidermis is largely regulated by [...] Read more.

Despite the constantly updated knowledge regarding the alterations occurring in the cells of patients with psoriasis, the status and the role of the lysosome, a control center of cell metabolism, remain to be elucidated. The architecture of the epidermis is largely regulated by the action of lysosomes, possibly activating signaling pathways in the cellular crosstalk of keratinocytes—epidermal cells—with infiltrating immune cells. Thus, in the present study, lysosome alterations were examined in vitro and in situ using a two-dimensional (2D) keratinocyte model of HaCaT cells with “psoriasis-like” inflammation and skin specimens, respectively. Specific fluorescence and immunohistochemical staining showed an augmented level of acidic organelles in response to keratinocyte activation (mimicking a psoriatic condition while maintaining the membrane integrity of these structures) as compared with the control, similar to that seen in skin samples taken from patients. Interestingly, patients with the most pronounced PASI (Psoriasis Area and Severity Index), BSA (Body Surface Area), and DLQI (Dermatology Life Quality Index) scores suffered a high incidence of positive lysosomal-associated membrane protein 1 (LAMP1) expression. Moreover, it was found that the gene deregulation pattern was comparable in lesioned (PP) and non-lesioned (PN) patient-derived skin tissue, which may indicate that these alterations occur prior to the onset of the characteristic phenotype of the disease. Changes in the activity of genes encoding the microphthalmia family (MiT family) of transcription factors and mammalian target of rapamycin complex 1 (MTORC1) were also observed in the in vitro psoriasis model, indicating that the biogenesis pathway of this arm is inhibited. Interestingly, in contrast to the keratinocytes of HaCaT with “psoriasis-like” inflammation, LAMP1 was up-regulated in both PP and PN skin, which can be a potential sign of an alternative mechanism of lysosome formation. Defining the molecular profile of psoriasis in the context of “the awesome lysosome” is not only interesting, but also desired; therefore, it is believed that this paper will serve to encourage other researchers to conduct further studies on this subject. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Pathology of Psoriasis)

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16 pages, 5258 KiB

Open AccessArticle

Infiltration of T Cells into a Three-Dimensional Psoriatic Skin Model Mimics Pathological Key Features

by Isabelle Lorthois, Mélissa Simard, Sophie Morin and Roxane Pouliot

Int. J. Mol. Sci. 2019, 20(7), 1670; https://doi.org/10.3390/ijms20071670 - 03 Apr 2019

Cited by 29 | Viewed by 4201

Abstract

Psoriasis is an autoimmune chronic dermatosis that is T cell-mediated, characterized by epidermal thickening, aberrant epidermal differentiation and inflammatory infiltrates, with a dominant Th1 and Th17 profile. Additional in vitro models are required to study the complex interactions between activated T cells and [...] Read more.

Psoriasis is an autoimmune chronic dermatosis that is T cell-mediated, characterized by epidermal thickening, aberrant epidermal differentiation and inflammatory infiltrates, with a dominant Th1 and Th17 profile. Additional in vitro models are required to study the complex interactions between activated T cells and skin cells, and to develop new, more effective treatments. We have therefore sought to model this psoriatic inflammation by the generation of tissue-engineered immunocompetent tissues, and we have investigated the response of activated T-cell infiltration in models produced with lesional psoriatic skin cells on major hallmarks of psoriasis. The immunocompetent lesional skin model displayed a delayed onset of epidermal differentiation, an hyperproliferation of the basal keratinocytes, a drastic increase in the secretion of proinflammatory cytokines, and a disturbed expression of key transcription factors, as observed in lesional plaques, suggesting a crucial importance of combining the pathological phenotype of cutaneous cells to T cells in order to generate a relevant model for psoriasis. Finally, we found this skin model to be responsive to methotrexate treatment, making it a valuable tool for drug development. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Pathology of Psoriasis)

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17 pages, 3130 KiB

Open AccessArticle

The Tissue-Engineered Human Psoriatic Skin Substitute: A Valuable In Vitro Model to Identify Genes with Altered Expression in Lesional Psoriasis

by Geneviève Rioux, Claudia Pouliot-Bérubé, Mélissa Simard, Manel Benhassine, Jacques Soucy, Sylvain L. Guérin and Roxane Pouliot

Int. J. Mol. Sci. 2018, 19(10), 2923; https://doi.org/10.3390/ijms19102923 - 26 Sep 2018

Cited by 19 | Viewed by 3636

Abstract

Psoriasis is a chronic inflammatory skin disease for which no cure has emerged. Its complex etiology requires the development of an in vitro model representative of the pathology. In this study, we exploited gene profiling analyses on microarray in order to characterize and [...] Read more.

Psoriasis is a chronic inflammatory skin disease for which no cure has emerged. Its complex etiology requires the development of an in vitro model representative of the pathology. In this study, we exploited gene profiling analyses on microarray in order to characterize and further optimize the production of a human psoriatic skin model representative of this in vivo skin disease. Various skin substitutes were produced by tissue-engineering using biopsies from normal, healthy donors, or from lesional or non-lesional skin samples from patients with psoriasis, and their gene expression profiles were examined by DNA microarray. We demonstrated that more than 3540 and 1088 genes (two-fold change) were deregulated between healthy/lesional and lesional/non-lesional psoriatic substitutes, respectively. Moreover, several genes related to lipid metabolism, such as PLA2G4E and PLA2G4C, were identified as repressed in the lesional substitutes. In conclusion, gene profiling analyses identified a list of deregulated candidate genes associated with various metabolic pathways that may contribute to the progression of psoriasis. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Pathology of Psoriasis)

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14 pages, 3516 KiB

Open AccessArticle

Oxidized Low-Density Lipoprotein-Deteriorated Psoriasis Is Associated with the Upregulation of Lox-1 Receptor and Il-23 Expression In Vivo and In Vitro

by Chun-Ming Shih, Chien-Yu Huang, Kuo-Hsien Wang, Chun-Yao Huang, Po-Li Wei, Yu-Jia Chang, Chi-Kun Hsieh, Kuan-Ting Liu and Ai-Wei Lee

Int. J. Mol. Sci. 2018, 19(9), 2610; https://doi.org/10.3390/ijms19092610 - 03 Sep 2018

Cited by 16 | Viewed by 3715

Abstract

Psoriasis is a chronic inflammatory skin disease. Even though scientists predict that abnormalities in lipid metabolism play an important role in the pathogenesis of psoriasis, the actual underlying mechanisms are still unclear. Therefore, understanding the possible relationship between mechanisms of the occurrence of [...] Read more.

Psoriasis is a chronic inflammatory skin disease. Even though scientists predict that abnormalities in lipid metabolism play an important role in the pathogenesis of psoriasis, the actual underlying mechanisms are still unclear. Therefore, understanding the possible relationship between mechanisms of the occurrence of psoriasis and dyslipidemia is an important issue that may lead to the development of effective therapies. Under this principle, we investigated the influences of hyperlipidemia in imiquimod (IMQ)-induced psoriasis-like B6.129S2-Apoe^tm1Unc/J mice and oxidized low-density lipoprotein (oxLDL) in tumor necrosis factor (TNF)-α-stimulated Hacat cells. In our study, we showed that a high-cholesterol diet aggravated psoriasis-like phenomena in IMQ-treated B6.129S2-Apoe^tm1Unc/J mice. In vitro analysis showed that oxLDL increased keratinocyte migration and lectin-type oxLDL receptor 1 (LOX-1) expression. Evidence suggested that interleukin (IL)-23 was a main cytokine in the pathogenesis of psoriasis. High-cholesterol diet aggravated IL-23 expression in IMQ-treated B6.129S2-Apoe^tm1Unc/J mice, and oxLDL induced IL-23 expression mediated by LOX-1 in TNF-α-stimulated Hacat cells. Therefore, it will be interesting to investigate the factors for the oxLDL induction of LOX-1 in psoriasis. LOX-1 receptor expression may be another novel treatment option for psoriasis and might represent the most promising strategy. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Pathology of Psoriasis)

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Review

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14 pages, 1703 KiB

Open AccessReview

The Significance of IL-36 Hyperactivation and IL-36R Targeting in Psoriasis

by Stefania Madonna, Giampiero Girolomoni, Charles A. Dinarello and Cristina Albanesi

Int. J. Mol. Sci. 2019, 20(13), 3318; https://doi.org/10.3390/ijms20133318 - 05 Jul 2019

Cited by 90 | Viewed by 7086

Abstract

Psoriasis is an immune-mediated inflammatory skin disease that involves mainly T helper (Th)17, Th1 and Th22 lymphocytes, which cause hyper-proliferation of the epidermis with aberrant differentiation of keratinocytes, and local production of chemokines and cytokines. These fuel a self-amplifying loop where these products [...] Read more.

Psoriasis is an immune-mediated inflammatory skin disease that involves mainly T helper (Th)17, Th1 and Th22 lymphocytes, which cause hyper-proliferation of the epidermis with aberrant differentiation of keratinocytes, and local production of chemokines and cytokines. These fuel a self-amplifying loop where these products act on T cells to perpetuate cutaneous inflammatory processes. Among the various inflammatory mediators involved, interleukin (IL)-36 cytokines are important for the recruitment and activation of neutrophils and Th17 cells in psoriatic skin. In particular, IL-36s induce chemokines and cytokines interfere with differentiation/cornification programs in the epidermis, as well as promote pathological angiogenesis and endothelial cell activation. IL-36 cytokines belong to the IL-1 family, and comprise IL-36α, IL-36β, and IL-36γ agonists as well as IL-36 receptor antagonist and IL-38 antagonists. IL-36 cytokines are up-regulated in psoriatic epidermis, and their expression is strongly induced by TNF-α and IL-17. Contrarily, IL-38 antagonist is downregulated, and its impaired expression may be relevant to the dysregulated inflammatory processes induced by IL-36. Here, we discuss on the pathogenic mechanisms leading to the altered balance of IL-36 agonists/antagonists and the significance of this dysregulation in psoriasis. Collection of the information will provide a theoretical basis for the development of novel therapeutic strategies based on IL-36 agonist/antagonist manipulation in psoriasis. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Pathology of Psoriasis)

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11 pages, 214 KiB

Open AccessReview

Proteomics in Psoriasis

by Leena Chularojanamontri, Norramon Charoenpipatsin, Narumol Silpa-Archa, Chanisada Wongpraparut and Visith Thongboonkerd

Int. J. Mol. Sci. 2019, 20(5), 1141; https://doi.org/10.3390/ijms20051141 - 06 Mar 2019

Cited by 17 | Viewed by 4477

Abstract

Psoriasis has been thought to be driven primarily by innate and adaptive immune systems that can be modified by genetic and environmental factors. Complex interplay between inflammatory cytokines and T-cells, especially Th1 and Th17 cells, leads to abnormal cell proliferation and psoriatic skin [...] Read more.

Psoriasis has been thought to be driven primarily by innate and adaptive immune systems that can be modified by genetic and environmental factors. Complex interplay between inflammatory cytokines and T-cells, especially Th1 and Th17 cells, leads to abnormal cell proliferation and psoriatic skin lesions. Nevertheless, such mechanisms do not entirely represent the pathogenesis of psoriasis. Moreover, earlier and better biomarkers in diagnostics, prognostics, and monitoring therapeutic outcomes of psoriasis are still needed. During the last two decades, proteomics (a systematic analysis of proteins for their identities, quantities, and functions) has been widely employed to psoriatic research. This review summarizes and discusses all of the previous studies that applied various modalities of proteomics technologies to psoriatic skin disease. The data obtained from such studies have led to (i) novel mechanisms and new hypotheses of the disease pathogenesis; (ii) biomarker discovery for diagnostics and prognostics; and (iii) proteome profiling for monitoring treatment efficacy and drug-induced toxicities. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Pathology of Psoriasis)

17 pages, 1936 KiB

Open AccessReview

Advances in Understanding the Immunological Pathways in Psoriasis

by Simona-Roxana Georgescu, Mircea Tampa, Constantin Caruntu, Maria-Isabela Sarbu, Cristina-Iulia Mitran, Madalina-Irina Mitran, Clara Matei, Carolina Constantin and Monica Neagu

Int. J. Mol. Sci. 2019, 20(3), 739; https://doi.org/10.3390/ijms20030739 - 10 Feb 2019

Cited by 96 | Viewed by 9628

Abstract

Psoriasis vulgaris is a chronic, immune-mediated, inflammatory, polygenic skin disorder affecting approximately 2% of the population. It has a great impact on quality of life; patients often experience depression, anxiety, stigma as well as suicidal behavior. Even though psoriasis is one of the [...] Read more.

Psoriasis vulgaris is a chronic, immune-mediated, inflammatory, polygenic skin disorder affecting approximately 2% of the population. It has a great impact on quality of life; patients often experience depression, anxiety, stigma as well as suicidal behavior. Even though psoriasis is one of the most studied dermatological conditions, the pathogenesis of the disease is still not completely elucidated. The complex interactions between keratinocytes, dendritic cells, T-lymphocytes, neutrophils and mast cells are responsible for the histopathological changes seen in psoriasis. The pathogenic model leading to the formation of psoriatic plaques has however evolved a lot over the years. There is now enough evidence to support the role of interleukin (IL) -23, IL-17, IL-22, T helper (Th) -17 cells, Th-22 cells, T regulatory cells, transforming growth factor (TGF)-β1 and IL-10 in the pathogenesis of the disease. Moreover, several inflammatory and anti-inflammatory molecules are currently being investigated, some of them showing promising results. The aim of this paper is to look over the most recent advances in the immunological pathways involved in the pathogenesis of psoriasis vulgaris. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Pathology of Psoriasis)

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Other

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2 pages, 1259 KiB

Open AccessCorrection

Correction: Bocheńska, K. et al. Lysosome Alterations in the Human Epithelial Cell Line HaCaT and Skin Specimens: Relevance to Psoriasis. Int. J. Mol. Sci. 2019, 20, 2255

by Katarzyna Bocheńska, Marta Moskot, Marcelina Malinowska, Joanna Jakóbkiewicz-Banecka, Aneta Szczerkowska-Dobosz, Dorota Purzycka-Bohdan, Joanna Pleńkowska, Bartosz Słomiński and Magdalena Gabig-Cimińska

Int. J. Mol. Sci. 2020, 21(2), 594; https://doi.org/10.3390/ijms21020594 - 16 Jan 2020

Cited by 4 | Viewed by 2140

Abstract

The authors wish to make the following corrections to this paper [...] Full article

(This article belongs to the Special Issue Molecular Mechanisms and Pathology of Psoriasis)

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