Critical Analysis of Cytoplasmic Progression of Inflammatory Signaling Suggests Potential Pharmacologic Targets for Wound Healing and Fibrotic Disorders DOI Creative Commons
Michael L. Samulevich, Liam E. Carman, Brian J. Aneskievich

и другие.

Biomedicines, Год журнала: 2024, Номер 12(12), С. 2723 - 2723

Опубликована: Ноя. 28, 2024

Successful skin wound healing is dependent on an interplay between epidermal keratinocytes and dermal fibroblasts as they react to local extracellular factors (DAMPs, PAMPs, cytokines, etc.) surveyed from that environment by numerous membrane receptors (e.g., TLRs, cytokine receptors, etc.). In turn, those are the start of a cytoplasmic signaling pathway where balance key effective and, needed, cell matrix regeneration. When directed through NF-κB, these routes lead transient responses benefit initiating immune recruitment, replication, chemokine production, protein synthesis. The converse can also occur, ongoing canonical NF-κB activation leads chronic, hyper-responsive states. Here, we assess three players, TAK1, TNFAIP3, TNIP1, in regulation activation, which, because their distinctive yet inter-related functions, either promote or limit activation. Their balanced function integral successful healing, given significant control over expression inflammation-, fibrosis-, remodeling-associated genes. Intriguingly, proteins have been emphasized dysregulated central systemic sclerosis (SSc). Notably, diffuse SSc shares some tissue features similar excessive inflammatory/fibrotic response without eventual resolution. Taking cue certain instances aberrant having shared aspects, e.g., chronic inflammation fibrosis, this review looks for first time, our knowledge, at what pathologies might common regarding progression NF-κB-mediated signaling. Additionally, while TNIP1 often investigated reported individually, propose them here whose consequences very highly interconnected focus NF-κB. We thus highlight emerging promise clinical derived improved understanding signal modulators. Depending protein, its indirect direct pharmacological has reported. Current findings support further intensive studies points both basic healthy cells well with goal targeting translational multiple cutaneous situations, whether stemming acute injury response.

Язык: Английский

Amlexanox ameliorates imiquimod-induced psoriasis-like dermatitis by inhibiting Th17 cells and the NF-κB signal pathway DOI Open Access
Juan Wu, Shan Liu, Hongwei Zhang

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2025, Номер 184, С. 117922 - 117922

Опубликована: Фев. 20, 2025

Язык: Английский

Процитировано

2
Interleukin-4 and Atopic Dermatitis: Why Does it Matter? A Narrative Review DOI Creative Commons
Tiago Torres, Pedro Mendes‐Bastos, Maria João Cruz

и другие.

Dermatology and Therapy, Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

Atopic dermatitis (AD) is a common chronic inflammatory skin condition that significantly impairs patients' quality of life as result intense itching and persistent eczematous lesions. Although AD has multifaceted etiology—including genetic predisposition, environmental triggers, barrier dysfunction, dysregulated immune responses—interleukin-4 (IL-4) recognized central role in its pathogenesis. This narrative review explores the IL-4 pathophysiology AD, contribution to atopic march, therapeutic impact inhibition. plays critical dysbiosis, pruritus, inflammation, all which contribute debilitating symptoms AD. Moreover, implicated other conditions, such asthma, allergic rhinitis, food allergies, underscoring beyond importance march. Recent advances targeted therapies, particularly IL-4/IL-13 signaling inhibitors, have changed management. Dupilumab, an receptor antagonist, demonstrated significant efficacy reducing enhancing patient outcomes both children adults. In addition symptomatic relief, suppressing may also offer potential for disease modification, altering AD's progression possibly preventing onset conditions. highlights crucial target By understanding pathogenesis exploring implications targeting pathways, this work can guide future research concerning treatment approaches emphasize need early interventions mitigate ultimately improve life.

Язык: Английский

Процитировано

1
Vitamin D: Beyond Traditional Roles—Insights into Its Biochemical Pathways and Physiological Impacts DOI Open Access
Vlad Mihai Voiculescu, Andreea Nelson Twakor,

Nicole Jerpelea

и другие.

Nutrients, Год журнала: 2025, Номер 17(5), С. 803 - 803

Опубликована: Фев. 26, 2025

Background: It is true that vitamin D did not earn its title as the "sunshine vitamin" for nothing. In recent years, however, there has been a shift in perception surrounding to type of hormone boasts countless bioactivities and health advantages. Historically, known take care skeletal integrity calcium-phosphorus balance body, but new scientific research displays much larger spectrum actions handled by this vitamin. Materials Methods: A systematic literature search was performed using following electronic databases: PubMed, Scopus, Web Science, Embase, Cochrane Library. Results: Many emerging ideas, especially concerning alternative hormonal pathways analogs, are uniformly challenging classic "one hormone-one receptor" hypothesis. To add more context this, receptor (VDR) previously assumed be only means through which biologically active steroid 1,25-dihydroxyvitamin D3 could impact body. Two other molecules apart from form 1,25(OH)2D3 have gained interest these reinvigorated on metabolism. These metabolites can interact with several nuclear receptors (like related orphan alpha-RORα, gamma-RORγ, aryl hydrocarbon receptor-AhR) trigger various biological responses. Conclusions: This paper thus makes case placing at forefront holistic dermatological investigating potential synergies between canonical noncanonical pathways. now plentiful opportunities manipulating understanding full actions, far beyond those minerals.

Язык: Английский

Процитировано

1
The Role of Keratinocytes in Skin Health and Disease DOI Open Access
Mohammed Saleh Al‐Dhubaibi, Ghada Farouk Mohammed, Saleh Salem Bahaj

и другие.

Dermatological Reviews, Год журнала: 2025, Номер 6(2)

Опубликована: Март 24, 2025

ABSTRACT Aim This study aims to provide a comprehensive analysis of keratinocytes, the predominant cell type in epidermis, by examining their structural, functional, and regulatory roles skin biology. The explores intricate processes keratinocyte differentiation, proliferation, immune interactions, emphasizing essential contributions homeostasis, wound healing, barrier integrity. Additionally, it investigates involvement keratinocytes dermatological disorders such as psoriasis, atopic dermatitis, cancer, highlighting pathological alterations molecular mechanisms. Methods review covers broad range studies, including vitro vivo research on biology, interactions with growth factors, inflammatory responses skin. It also discusses therapeutic advancements biologics gene therapy that focus restoring function diseases. Results highlights play pivotal role inflammation regulation factors promote healing regeneration. Dysregulation is linked several diseases, need for targeted approaches. Recent treatments, biologics, offer promising outcomes managing conditions driven dysfunction. Conclusion primary aim this an in‐depth overview functions particularly health, inflammation, disease development. highlight latest strategies targeting treatment

Язык: Английский

Процитировано

1
Keratinocytes: new perspectives in inflammatory skin diseases DOI
Jinghan Ye, Yuping Lai

Trends in Molecular Medicine, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

1
IFN-γ/TNF-α Synergism Induces Pro-Inflammatory Cytokine and Chemokine Production by In Vitro Canine Keratinocytes DOI Creative Commons
Kyungsook Jung, Ji‐Yeong Ku,

Jang-Woo Kwon

и другие.

Veterinary Sciences, Год журнала: 2025, Номер 12(1), С. 55 - 55

Опубликована: Янв. 14, 2025

Activated keratinocytes play a crucial role in skin inflammation through the production of multiple inflammatory mediators; however, little is known about cytokine secretion by activated dogs. This study aimed to investigate effects Th1 and Th2 types cytokines on keratinocyte-derived mediators. Canine progenitor epidermal (CPEKs) were incubated with canine recombinant IL-4, IL-13, an IL4/IL13 mixture, IFN-γ, TNF-α, or IFN-γ/TNF-α mixture for 24 h following 100% confluency. Culture supernatants analyzed concentration, including chemokine ligand (CXCL) 8, IL-10, IL-6, IL-1ß, IL-12, 2 (CCL2) enzyme-linked immunosorbent assay. CPEKs showed significantly increased IL-6 concentration. In addition, concentrations CXCL8 detected TNF-α mixture. CCL2 cells The synergistically enhanced production. Dose-dependent elevations also observed response These findings indicate that IFN-γ increase pro-inflammatory chemokines secreted keratinocytes. vitro culture system could be useful cytokine-mediated crosstalk between immune new therapeutic strategies keratinocyte-mediated diseases.

Язык: Английский

Процитировано

0
Regulation of epithelial growth factor receptors by the oncoprotein E5 during the HPV16 differentiation-dependent life cycle DOI Creative Commons
Mariano A. Molina,

Sneha Biswas,

Omar Jiménez-Vázquez

и другие.

Tumour Virus Research, Год журнала: 2025, Номер 19, С. 200315 - 200315

Опубликована: Март 7, 2025

Human papillomavirus (HPV) 16 infection initiates upon viral entry into the basal cells of epithelium. The virus manipulates signaling pathways to complete its life cycle, which depends on cellular differentiation. expresses oncoproteins E5, E6, and E7 promote immune evasion, cell cycle progression, apoptosis inhibition, replication. least studied oncoprotein is E5 (16E5), can regulate epithelial growth factor receptor (GFR) pathways. GFRs such as transforming factor-beta (TGFBR), epidermal (EGFR), keratinocyte (KGFR) have essential roles in growth, differentiation, proliferation. These receptors obtain their ligands from microenvironment, once activated, behavior therefore represent valuable targets for establish maintain a environment supportive infection. ability 16E5 proliferation differentiation varies through differentiating epithelium, making it necessary adequately describe association between GFRs. Here we summarize regulation GFR by 16E5, discuss stromal factors, outline unresolved questions over during HPV cycle.

Язык: Английский

Процитировано

0
Role of Formyl Peptide Receptor 2 and Toll-Like Receptor 2 in Skin Barrier Function and Atopic Dermatitis DOI Creative Commons

Marco Lebtig,

Andreas Peschel, Dorothee Kretschmer

и другие.

Journal of Investigative Dermatology, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

The skin acts as a barrier against external threats and plays an important role in tissue repair. Skin cells, including keratinocytes, sense microbe-associated molecular pattern molecules released by members of the bacterial microbiome, cellular responses control central processes homeostasis or inflammation. How combination amount different patterns modulate cell functions is not yet fully understood. Here, we review current knowledge cells to patterns, focusing on Toll-like receptor 2 formyl peptide 2, two most receptors for sensing microbiome.

Язык: Английский

Процитировано

0
Unrestrained MyD88 signaling in A20-deficient keratinocytes triggers T cell dependent Psoriatic Arthritis like disease DOI

Raymond Tobias,

Sugandh Kumar, Jared Liu

и другие.

Journal of Investigative Dermatology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Cutaneous T cell immunity DOI
Pirooz Zareie, E. H. Weiss, Daniel H. Kaplan

и другие.

Nature Immunology, Год журнала: 2025, Номер unknown

Опубликована: Май 7, 2025

Язык: Английский

Процитировано

0