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Advanced Research of Skin Inflammation and Related Diseases
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Advanced Research of Skin Inflammation and Related Diseases

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: 20 January 2025 | Viewed by 9473

Special Issue Editors

Dr. Filomena Napolitano

E-Mail Website
Guest Editor
Department of Translational Medical Sciences, University of Naples “Federico II”, 80131 Naples, Italy
Interests: in vitro models for skin inflammation and fibrosis; systemic sclerosis; new therapeutic approach for skin disorders
Dr. Valentina Giudice

E-Mail Website
Guest Editor
Department of Medicine and Surgery, University of Salerno, 84081 Baronissi, Italy
Interests: hematology; flow cytometry; immunology

Special Issue Information

Dear Colleagues,

Skin inflammation has many possible causes, including infections, allergies, and autoimmune diseases. During inflammation, the skin undergoes substantial changes: immune cells infiltrate the dermis and epidermis; keratinocytes, fibroblasts, and immune cells release a large amount of pro-inflammatory cytokines; and fibroblasts and myofibroblasts synthetize and deposit excessive components of the extracellular matrix, leading to fibrosis or scarring. In the last decades, numerous signalling proteins and microRNAs have been associated with chronic inflammatory conditions. Future studies should provide a systematic picture of the molecular mechanisms underlying skin inflammation; in particular, the evaluation of crosstalk between different cell types in the epidermis, dermis, and subcutaneous layers during inflammation should be performed.

In this Special Issue for IJMS, we will focus on molecular studies in biology and medicine as a promising approach to identify new therapeutic targets, as well as novel biomarkers with diagnostic significance in skin pathologies. In vitro data, human studies, and clinical observations in all fields of basic immune and skin inflammation research are welcome.

Dr. Filomena Napolitano
Dr. Valentina Giudice
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • skin
  • inflammation
  • molecular target
  • inflammatory skin diseases
  • psoriasis
  • urticaria
  • atopic dermatitis
  • systemic sclerosis
  • skin fibrosis
  • immune system

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Published Papers (5 papers)

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Research

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14 pages, 3780 KiB  
Article
The Crosstalk between N-Formyl Peptide Receptors and uPAR in Systemic Sclerosis: Molecular Mechanisms, Pathogenetic Role and Therapeutic Opportunities
by Filomena Napolitano, Francesca Wanda Rossi, Amato de Paulis, Antonio Lavecchia and Nunzia Montuori
Int. J. Mol. Sci. 2024, 25(6), 3156; https://doi.org/10.3390/ijms25063156 - 9 Mar 2024
Viewed by 1042
Abstract
Systemic Sclerosis (SSc) is a heterogeneous autoimmune disease characterized by widespread vasculopathy, the presence of autoantibodies and the progressive fibrosis of skin and visceral organs. There are still many questions about its pathogenesis, particularly related to the complex regulation of the fibrotic process, [...] Read more.
Systemic Sclerosis (SSc) is a heterogeneous autoimmune disease characterized by widespread vasculopathy, the presence of autoantibodies and the progressive fibrosis of skin and visceral organs. There are still many questions about its pathogenesis, particularly related to the complex regulation of the fibrotic process, and to the factors that trigger its onset. Our recent studies supported a key role of N-formyl peptide receptors (FPRs) and their crosstalk with uPAR in the fibrotic phase of the disease. Here, we found that dermal fibroblasts acquire a proliferative phenotype after the activation of FPRs and their interaction with uPAR, leading to both Rac1 and ERK activation, c-Myc phosphorylation and Cyclin D1 upregulation which drive cell cycle progression. The comparison between normal and SSc fibroblasts reveals that SSc fibroblasts exhibit a higher proliferative rate than healthy control, suggesting that an altered fibroblast proliferation could contribute to the initiation and progression of the fibrotic process. Finally, a synthetic compound targeting the FPRs/uPAR interaction significantly inhibits SSc fibroblast proliferation, paving the way for the development of new targeted therapies in fibrotic diseases. Full article
(This article belongs to the Special Issue Advanced Research of Skin Inflammation and Related Diseases)
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17 pages, 3928 KiB  
Article
The Alarmin Triad—IL-25, IL-33, and TSLP—Serum Levels and Their Clinical Implications in Chronic Spontaneous Urticaria
by Carmen-Teodora Dobrican-Băruța, Diana Mihaela Deleanu, Ioana Adriana Muntean, Irena Nedelea, Radu-Gheorghe Bălan, Gabriela Adriana Filip and Lucia Maria Procopciuc
Int. J. Mol. Sci. 2024, 25(4), 2026; https://doi.org/10.3390/ijms25042026 - 7 Feb 2024
Cited by 3 | Viewed by 1519
Abstract
This study delves into the critical role of alarmins in chronic spontaneous urticaria (CSU), focusing on their impact on disease severity and the quality of life (QoL) of patients. We investigated the alterations in alarmin levels in CSU patients and their correlations with [...] Read more.
This study delves into the critical role of alarmins in chronic spontaneous urticaria (CSU), focusing on their impact on disease severity and the quality of life (QoL) of patients. We investigated the alterations in alarmin levels in CSU patients and their correlations with the Urticaria Activity Score (UAS7) and the Dermatology Life Quality Index (DLQI). We analyzed serum levels of interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP) in 50 CSU patients, comparing these to 38 healthy controls. The study examined the relationship between alarmin levels and clinical outcomes, including disease severity and QoL. Elevated levels of IL-33 and TSLP in CSU patients (p < 0.0001) highlight their potential role in CSU pathogenesis. Although IL-25 showed higher levels in CSU patients, this did not reach statistical significance (p = 0.0823). Crucially, IL-33’s correlation with both UAS7 and DLQI scores underscores its potential as a biomarker for CSU diagnosis and severity assessment. Of the alarmins analyzed, IL-33 emerges as particularly significant for further exploration as a diagnostic and prognostic biomarker in CSU. Its substantial correlation with disease severity and impact on QoL makes it a compelling candidate for future research, potentially serving as a target for therapeutic interventions. Given these findings, IL-33 deserves additional investigation to confirm its role and effectiveness as a biomarker and therapeutic target in CSU. Full article
(This article belongs to the Special Issue Advanced Research of Skin Inflammation and Related Diseases)
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18 pages, 7035 KiB  
Article
The Development of Human Ex Vivo Models of Inflammatory Skin Conditions
by Eddy Hsi Chun Wang, Rebecca Barresi-Thornton, Li-Chi Chen, Maryanne Makredes Senna, I-Chien Liao, Ying Chen, Qian Zheng and Charbel Bouez
Int. J. Mol. Sci. 2023, 24(24), 17255; https://doi.org/10.3390/ijms242417255 - 8 Dec 2023
Cited by 1 | Viewed by 2197
Abstract
Traditional research in inflammatory dermatoses has relied on animal models and reconstructed human epidermis to study these conditions. However, these models are limited in replicating the complexity of real human skin and reproducing the intricate pathological changes in skin barrier components and lipid [...] Read more.
Traditional research in inflammatory dermatoses has relied on animal models and reconstructed human epidermis to study these conditions. However, these models are limited in replicating the complexity of real human skin and reproducing the intricate pathological changes in skin barrier components and lipid profiles. To address this gap, we developed experimental models that mimic various human inflammatory skin phenotypes. Human ex vivo skins were stimulated with various triggers, creating models for inflammation-induced angiogenesis, irritation response, and chronic T-cell activation. We assessed the alterations in skin morphology, cellular infiltrates, cytokine production, and epidermal lipidomic profiles. In the pro-angiogenesis model, we observed increased mast cell degranulation and elevated levels of angiogenic growth factors. Both the irritant and chronic inflammation models exhibited severe epidermal disruption, along with macrophage infiltration, leukocyte exocytosis, and heightened cytokine levels. Lipidomic analysis revealed minor changes in the pro-angiogenesis model, whereas the chronic inflammation and irritant models exhibited significant decreases in barrier essential ceramide subclasses and a shift toward shorter acyl chain lengths (<C18), indicating skin barrier instability. Additionally, the irritant and chronic inflammation models are responsive to immunosuppressants. These models hold promise for advancing scientific understanding and the development of therapeutic and skincare solutions for individuals afflicted by compromised skin conditions. Full article
(This article belongs to the Special Issue Advanced Research of Skin Inflammation and Related Diseases)
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18 pages, 2327 KiB  
Article
Identifying Serum Metabolomic Markers Associated with Skin Disease Activity in Patients with Psoriatic Arthritis
by Hani Choksi, Shenghan Li, Nikita Looby, Max Kotlyar, Igor Jurisica, Vathany Kulasingam and Vinod Chandran
Int. J. Mol. Sci. 2023, 24(20), 15299; https://doi.org/10.3390/ijms242015299 - 18 Oct 2023
Cited by 4 | Viewed by 1895
Abstract
Psoriatic arthritis (PsA) is a chronic, systemic, immune-mediated inflammatory disease causing cutaneous and musculoskeletal inflammation that affects 25% of patients with psoriasis. Current methods for evaluating PsA disease activity are not accurate enough for precision medicine. A metabolomics-based approach can elucidate psoriatic disease [...] Read more.
Psoriatic arthritis (PsA) is a chronic, systemic, immune-mediated inflammatory disease causing cutaneous and musculoskeletal inflammation that affects 25% of patients with psoriasis. Current methods for evaluating PsA disease activity are not accurate enough for precision medicine. A metabolomics-based approach can elucidate psoriatic disease pathogenesis, providing potential objective biomarkers. With the hypothesis that serum metabolites are associated with skin disease activity, we aimed to identify serum metabolites associated with skin activity in PsA patients. We obtained serum samples from patients with PsA (n = 150) who were classified into mild, moderate and high disease activity groups based on the Psoriasis Area Severity Index. We used solid-phase microextraction (SPME) for sample preparation, followed by data acquisition via an untargeted liquid chromatography—mass spectrometry (LC-MS) approach. Disease activity levels were predicted using identified metabolites and machine learning algorithms. Some metabolites tentatively identified include eicosanoids with anti- or pro-inflammatory properties, like 12-Hydroxyeicosatetraenoic acid, which was previously implicated in joint disease activity in PsA. Other metabolites of interest were associated with dysregulation of fatty acid metabolism and belonged to classes such as bile acids, oxidized phospholipids, and long-chain fatty acids. We have identified potential metabolites associated with skin disease activity in PsA patients. Full article
(This article belongs to the Special Issue Advanced Research of Skin Inflammation and Related Diseases)
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Review

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13 pages, 1543 KiB  
Review
The Benefits of Water from Nitrodi’s Spring: The In Vitro Studies Leading the Potential Clinical Applications
by Ilaria Mormile, Fabiana Tuccillo, Francesca Della Casa, Valentina D’Aiuto, Nunzia Montuori, Marina De Rosa, Filomena Napolitano, Amato de Paulis and Francesca Wanda Rossi
Int. J. Mol. Sci. 2023, 24(18), 13685; https://doi.org/10.3390/ijms241813685 - 5 Sep 2023
Cited by 3 | Viewed by 1654
Abstract
Natural products (water, plants, and minerals) have been studied for diverse applications in health and disease. Since there has been a growing interest in the introduction of thermal water as a clinical complementary approach in the treatment of low-grade inflammation and stress-related conditions, [...] Read more.
Natural products (water, plants, and minerals) have been studied for diverse applications in health and disease. Since there has been a growing interest in the introduction of thermal water as a clinical complementary approach in the treatment of low-grade inflammation and stress-related conditions, this review focuses on the oldest spa in the world: Nitrodi’s spring. Substantial studies in the 1960s showed that both the internal and external use of Nitrodi’s water yielded several benefits in physiological processes and in treating certain disorders, mainly allergic and autoimmune inflammatory conditions. More recently, a novel interest in Nitrodi’s water has prompted researchers to further explore the effects of this water and shed light on the molecular mechanisms sustaining its therapeutic efficacy. In different epithelial cell models, Nitrodi’s water had strong promotional effects on proliferation, cell migration, cell viability, and fibroblast to myofibroblast transition, all of which essential for wound healing and tissue remodeling. Moreover, Nitrodi’s water exhibited anti-oxidant and anti-inflammatory properties through the inhibition of ROS production and protein S-nitrosylation. Here, we have collected the clinical and basic data on Nitrodi’s water and reviewed articles that have discussed its use as a potential treatment for several inflammatory and autoimmune diseases and age-related skin deterioration. Full article
(This article belongs to the Special Issue Advanced Research of Skin Inflammation and Related Diseases)
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