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Inflammatory Skin Conditions 2020

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 75646

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Prof. Dr. Christopher Jackson

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Guest Editor

Sutton Arthritis Research Laboratory, Kolling Institute, University of Sydney at Royal North Shore Hospital, Sydney, Australia
Interests: inflammation; chronic wounds; rheumatoid arthritis; skin; activated protein C; matrix metalloproteinases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The skin provides a barrier to protect the body from environmental insults, including pathogens, as well as maintaining temperature, and control evaporation. It comprises the epidermis, composed mainly of keratinocytes and the dermis, housing largely fibroblasts, blood vessels and matrix. Breaches of this barrier are common events, however, the inability to restore this barrier function can result in common health problems which have high morbidity and in some cases mortality. This diverse group of diseases includes acne, rosacea, atopic dermatitis, psoriasis, chronic wounds, blistering diseases and toxic epidermal necrolysis. Although these may be grouped under a single heading of inflammatory skin disorders there are many different molecular pathways involved, including multiple soluble mediators and cellular receptors as well as signalling molecules such as NF-kB, mTOR, MAP kinases and Akt. Understanding these molecular mechanisms are a vital step to providing new and innovative approaches to dampen inflammation and restore the defective barrier to better treat and ultimately cure these recalcitrant conditions.

This Special Issue calls for original research, full reviews, and perspectives that address the progress and current knowledge in the overlapping research topics of inflammatory skin conditions. These include but are not limited to the fields that are mentioned in the keywords.

Prof. Dr. Christopher Jackson
Guest Editor

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Keywords

inflammatory skin conditions
chronic wounds
psoriasis
dermatitis
epidermis
molecular signalling
cellular receptors
keratinocytes
angiogenesis
barrier function
inflammatory cells
immunity

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Related Special Issues

Inflammatory Skin Conditions in International Journal of Molecular Sciences (30 articles)
Inflammatory Skin Conditions 2017 in International Journal of Molecular Sciences (13 articles)
Inflammatory Skin Conditions 2018 in International Journal of Molecular Sciences (12 articles)

Published Papers (10 papers)

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Research

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13 pages, 2564 KiB

Open AccessArticle

Immunological Memory in Imiquimod-Induced Murine Model of Psoriasiform Dermatitis

by Kevin Fenix, Danushka K. Wijesundara, Allison J. Cowin, Branka Grubor-Bauk and Zlatko Kopecki

Int. J. Mol. Sci. 2020, 21(19), 7228; https://doi.org/10.3390/ijms21197228 - 30 Sep 2020

Cited by 22 | Viewed by 3656

Abstract

Psoriasis is a common chronic inflammatory skin condition manifested by T cell responses and characterized by preferential recurrence at previously inflamed sites upon withdrawal of treatment. The site-specific disease memory in psoriasis has been linked to CD8⁺CD103⁺ tissue-resident memory T cells (Trm) in the epidermis which were previously thought to only provide “frontline” protection against pathogens and immunosurveillance during cancer development. In this study, we correlated the presence of a subset of the Trm cells which are also CD49a⁺ with disease severity in human psoriatic lesions with acute and chronic disease. Using an imiquimod (IMQ)-induced murine model of psoriasiform dermatitis, we also investigated the level of CD49a⁺ Trm cells in acute, chronic and resolved psoriatic lesions. Investigation of clinical human samples showed that patient disease severity highly correlated with the numbers of epidermal CD49a⁺ Trm cells. Additionally, this subset of Trm cells was shown to persist in resolved lesions of murine psoriasiform dermatitis once clinical disease features had subsided. Importantly, these CD49a⁺ Trm cells showed significantly higher levels of granzyme B (GzmB) production compared to acute disease, suggesting a potential role of CD49a⁺ Trm cells for psoriatic re-occurrence in resolved patients. Better understanding of epidermal CD49a⁺ Trm cell activity is necessary for development of advanced treatment strategies for psoriasis to permit long-term, continuous disease control. Full article

(This article belongs to the Special Issue Inflammatory Skin Conditions 2020)

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22 pages, 19285 KiB

Open AccessArticle

From Inflammation to Cutaneous Repair: Topical Application of Lupeol Improves Skin Wound Healing in Rats by Modulating the Cytokine Levels, NF-κB, Ki-67, Growth Factor Expression, and Distribution of Collagen Fibers

by Fernando Pereira Beserra, Lucas Fernando Sérgio Gushiken, Ana Júlia Vieira, Danilo Augusto Bérgamo, Patrícia Luísa Bérgamo, Mariana Oliveira de Souza, Carlos Alberto Hussni, Regina Kiomi Takahira, Rafael Henrique Nóbrega, Emanuel Ricardo Monteiro Martinez, Christopher John Jackson, Gabriela Lemos de Azevedo Maia, Ariane Leite Rozza and Cláudia Helena Pellizzon

Int. J. Mol. Sci. 2020, 21(14), 4952; https://doi.org/10.3390/ijms21144952 - 13 Jul 2020

Cited by 54 | Viewed by 5822

Abstract

Skin wound healing is a highly complex event that involves different mediators at the cellular and molecular level. Lupeol has been reported to possess different biological activities, such as anti-inflammatory, antioxidant, antidiabetic, and in vitro wound healing properties, which motivated us to proceed with in vivo studies. We aimed to investigate the wound healing effect of lupeol-based cream for 3, 7, and 14 days. Wound excisions were induced on the thoraco-lumbar region of rats and topically treated immediately after injury induction. Macroscopic, histopathological, and immunohistochemical analyses were performed. Cytokine levels were measured by ELISA and gene expression was evaluated by real-time RT-qPCR. Our results showed a strong wound-healing effect of lupeol-based cream after 7 and 14 days. Lupeol treatment caused a reduction in proinflammatory cytokines (TNF-a, IL-1β, and IL-6) and gene and protein NF-κB expression, and positively altered IL-10 levels, showing anti-inflammatory effects in the three treatment periods. Lupeol treatment showed involvement in the proliferative phase by stimulating the formation of new blood vessels, increasing the immunostaining of Ki-67 and gene expression, and immunolabeling of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), and increasing gene expression of transforming growth factor beta-1 (TGF-β1) after seven days of treatment. Lupeol was also involved in the tissue regeneration phase by increasing the synthesis of collagen fibers noted in the three treatment periods analyzed. Our findings suggest that lupeol may serve as a novel therapeutic option to treat cutaneous wounds by regulating mechanisms involved in the inflammatory, proliferative, and tissue-remodeling phases. Full article

(This article belongs to the Special Issue Inflammatory Skin Conditions 2020)

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Review

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13 pages, 774 KiB

Open AccessReview

Updates on the Risk of Neuropsychiatric and Gastrointestinal Comorbidities in Rosacea and Its Possible Relationship with the Gut–Brain–Skin Axis

by Yu Ri Woo, Yu Jin Han, Hei Sung Kim, Sang Hyun Cho and Jeong Deuk Lee

Int. J. Mol. Sci. 2020, 21(22), 8427; https://doi.org/10.3390/ijms21228427 - 10 Nov 2020

Cited by 27 | Viewed by 5000

Abstract

Rosacea is a common chronic cutaneous inflammatory disorder. Recently, patients with rosacea were identified as having a higher risk of developing various comorbidities such as cardiovascular disease, psychiatric disorders, neurologic disorders, and gastrointestinal disorders. However, the risks of some comorbidities in patients with rosacea are somewhat contradictory, depending upon the study design. Moreover, pathomechanisms associated with the comorbidities of patients with rosacea remain poorly elucidated. The purpose of this review was to provide the most up-to-date evidence on the risks of neuropsychiatric and gastrointestinal comorbidities in patients with rosacea. Moreover, the molecular pathomechanisms associated with neuropsychiatric and gastrointestinal comorbidities in patients with rosacea were evaluated based on recent studies. This review was also intended to focus more on the role of the gut–brain–skin axis in the association of neuropsychiatric and gastrointestinal comorbidities in rosacea. Full article

(This article belongs to the Special Issue Inflammatory Skin Conditions 2020)

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28 pages, 867 KiB

Open AccessReview

Advanced Medical Therapies in the Management of Non-Scarring Alopecia: Areata and Androgenic Alopecia

by Antonio Martinez-Lopez, Trinidad Montero-Vilchez, Álvaro Sierra-Sánchez, Alejandro Molina-Leyva and Salvador Arias-Santiago

Int. J. Mol. Sci. 2020, 21(21), 8390; https://doi.org/10.3390/ijms21218390 - 9 Nov 2020

Cited by 21 | Viewed by 10329

Abstract

Alopecia is a challenging condition for both physicians and patients. Several topical, intralesional, oral, and surgical treatments have been developed in recent decades, but some of those therapies only provide partial improvement. Advanced medical therapies are medical products based on genes, cells, and/or tissue engineering products that have properties in regenerating, repairing, or replacing human tissue. In recent years, numerous applications have been described for advanced medical therapies. With this background, those therapies may have a role in the treatment of various types of alopecia such as alopecia areata and androgenic alopecia. The aim of this review is to provide dermatologists an overview of the different advanced medical therapies that have been applied in the treatment of alopecia, by reviewing clinical and basic research studies as well as ongoing clinical trials. Full article

(This article belongs to the Special Issue Inflammatory Skin Conditions 2020)

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28 pages, 33211 KiB

Open AccessReview

From Grafts to Human Bioengineered Vascularized Skin Substitutes

by Wasima Oualla-Bachiri, Ana Fernández-González, María I. Quiñones-Vico and Salvador Arias-Santiago

Int. J. Mol. Sci. 2020, 21(21), 8197; https://doi.org/10.3390/ijms21218197 - 2 Nov 2020

Cited by 43 | Viewed by 6737

Abstract

The skin plays an important role in the maintenance of the human’s body physiological homeostasis. It acts as a coverage that protects against infective microorganism or biomechanical impacts. Skin is also implied in thermal regulation and fluid balance. However, skin can suffer several damages that impede normal wound-healing responses and lead to chronic wounds. Since the use of autografts, allografts, and xenografts present source limitations and intense rejection associated problems, bioengineered artificial skin substitutes (BASS) have emerged as a promising solution to address these problems. Despite this, currently available skin substitutes have many drawbacks, and an ideal skin substitute has not been developed yet. The advances that have been produced on tissue engineering techniques have enabled improving and developing new arising skin substitutes. The aim of this review is to outline these advances, including commercially available skin substitutes, to finally focus on future tissue engineering perspectives leading to the creation of autologous prevascularized skin equivalents with a hypodermal-like layer to achieve an exemplary skin substitute that fulfills all the biological characteristics of native skin and contributes to wound healing. Full article

(This article belongs to the Special Issue Inflammatory Skin Conditions 2020)

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28 pages, 1051 KiB

Open AccessReview

The Risk of Systemic Diseases in Those with Psoriasis and Psoriatic Arthritis: From Mechanisms to Clinic

by Yu Ri Woo, Chul Jong Park, Hoon Kang and Jung Eun Kim

Int. J. Mol. Sci. 2020, 21(19), 7041; https://doi.org/10.3390/ijms21197041 - 24 Sep 2020

Cited by 31 | Viewed by 5790

Abstract

Psoriasis and psoriatic arthritis (PsA) have been recently considered as chronic systemic inflammatory disorders. Over the past decades, enormous evidence indicates that patients with psoriasis and PsA have a higher risk of developing various comorbidities including cardiovascular disease, metabolic disease, cancers, infections, autoimmune disease, and psychiatric diseases. However, reported risks of some comorbidities in those with psoriasis and PsA are somewhat different according to the research design. Moreover, pathomechanisms underlying comorbidities of those with psoriasis and PsA remain poorly elucidated. The purpose of this review is to provide the most updated comprehensive view of the risk of systemic comorbidities in those with psoriasis and PsA. Molecular mechanisms associated with the development of various comorbidities in those with psoriasis and PsA are also reviewed based on recent laboratory and clinical investigations. Identifying the risk of systemic comorbidities and its associated pathomechanisms in those with psoriasis and PsA could provide a sufficient basis to use a multi-disciplinary approach for treating patients with psoriasis and PsA. Full article

(This article belongs to the Special Issue Inflammatory Skin Conditions 2020)

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13 pages, 872 KiB

Open AccessReview

Histopathologic Features of Lymphedema: A Molecular Review

by Claire Y. Li, Raghu P. Kataru and Babak J. Mehrara

Int. J. Mol. Sci. 2020, 21(7), 2546; https://doi.org/10.3390/ijms21072546 - 6 Apr 2020

Cited by 46 | Viewed by 6274

Abstract

An estimated 5 million people in the United States are affected by secondary lymphedema, with most cases attributed to malignancies or malignancy-related treatments. The pathogenesis of secondary lymphedema has historically been attributed to lymphatic injury or dysfunction; however, recent studies illustrate the complexity of lymphedema as a disease process in which many of its clinical features such as inflammation, fibrosis, adipogenesis, and recurrent infections contribute to on-going lymphatic dysfunction in a vicious cycle. Investigations into the molecular underpinning of these features further our understanding of the pathophysiology of this disease and suggests new therapeutics. Full article

(This article belongs to the Special Issue Inflammatory Skin Conditions 2020)

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13 pages, 780 KiB

Open AccessReview

The Role of the Cutaneous Microbiome in Hidradenitis Suppurativa—Light at the End of the Microbiological Tunnel

by Ewan A. Langan, Andreas Recke, Therezia Bokor-Billmann, Franck Billmann, Birgit K. Kahle and Detlef Zillikens

Int. J. Mol. Sci. 2020, 21(4), 1205; https://doi.org/10.3390/ijms21041205 - 11 Feb 2020

Cited by 29 | Viewed by 13403

Abstract

The development of next generation sequencing, coupled with advances in bio-informatics, has provided new insights into the role of the cutaneous microbiome in the pathophysiology of a range of inflammatory skin diseases. In fact, it has even been suggested that the identification of specific skin microbial signatures may not only be useful in terms of diagnosis of skin diseases but they may also ultimately help inform personalised treatment strategies. To date, research investigating the role of microbiota in the development of inflammatory skin diseases has largely focused on atopic eczema and psoriasis vulgaris. The role of the microbiome in Hidradenits suppurativa (HS)—also known as acne inversa—a chronic auto-inflammatory skin disease associated with significant morbidity, has received comparatively little attention. This is despite the fact that antimicrobial therapy plays a central role in the treatment of HS. After briefly outlining the clinical features of HS and current treatment strategies, we move on to review the evidence of microbial dysbiosis in HS pathophysiology. We conclude by outlining the potential for metagenomic studies to deepen our understanding of HS biology but more importantly to identify novel and much needed treatment strategies. Full article

(This article belongs to the Special Issue Inflammatory Skin Conditions 2020)

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39 pages, 933 KiB

Open AccessReview

Review—Current Concepts in Inflammatory Skin Diseases Evolved by Transcriptome Analysis: In-Depth Analysis of Atopic Dermatitis and Psoriasis

by Julius Schwingen, Mustafa Kaplan and Florian C. Kurschus

Int. J. Mol. Sci. 2020, 21(3), 699; https://doi.org/10.3390/ijms21030699 - 21 Jan 2020

Cited by 49 | Viewed by 8912

Abstract

During the last decades, high-throughput assessment of gene expression in patient tissues using microarray technology or RNA-Seq took center stage in clinical research. Insights into the diversity and frequency of transcripts in healthy and diseased conditions provide valuable information on the cellular status in the respective tissues. Growing with the technique, the bioinformatic analysis toolkit reveals biologically relevant pathways which assist in understanding basic pathophysiological mechanisms. Conventional classification systems of inflammatory skin diseases rely on descriptive assessments by pathologists. In contrast to this, molecular profiling may uncover previously unknown disease classifying features. Thereby, treatments and prognostics of patients may be improved. Furthermore, disease models in basic research in comparison to the human disease can be directly validated. The aim of this article is not only to provide the reader with information on the opportunities of these techniques, but to outline potential pitfalls and technical limitations as well. Major published findings are briefly discussed to provide a broad overview on the current findings in transcriptomics in inflammatory skin diseases. Full article

(This article belongs to the Special Issue Inflammatory Skin Conditions 2020)

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15 pages, 2738 KiB

Open AccessReview

Derailed Ceramide Metabolism in Atopic Dermatitis (AD): A Causal Starting Point for a Personalized (Basic) Therapy

by Markus Blaess and Hans-Peter Deigner

Int. J. Mol. Sci. 2019, 20(16), 3967; https://doi.org/10.3390/ijms20163967 - 15 Aug 2019

Cited by 23 | Viewed by 9101

Abstract

Active rebuilding, stabilizing, and maintaining the lipid barrier of the skin is an encouraging disease management and care concept for dry skin, atopic dermatitis (eczema, neurodermatitis), and psoriasis. For decades, corticosteroids have been the mainstay of topical therapy for atopic dermatitis; however, innovations within the scope of basic therapy are rare. In (extremely) dry, irritated, or inflammatory skin, as well as in lesions, an altered (sphingo)lipid profile is present. Recovery of a balanced (sphingo)lipid profile is a promising target for topical and personalized treatment and prophylaxis. New approaches for adults and small children are still lacking. With an ingenious combination of commonly used active ingredients, it is possible to restore and reinforce the dermal lipid barrier and maintain refractivity. Lysosomes and ceramide de novo synthesis play a key role in attenuation of the dermal lipid barrier. Linoleic acid in combination with amitriptyline in topical medication offers the possibility to relieve patients affected by dry and itchy skin, mild to moderate atopic dermatitis lesions, and eczemas without the commonly occurring serious adverse effects of topical corticosteroids or systemic antibody administration. Full article

(This article belongs to the Special Issue Inflammatory Skin Conditions 2020)

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