IL33: Roles in Allergic Inflammation and Therapeutic Perspectives

Frontiers in Immunology, Год журнала: 2019, Номер 10

Опубликована: Март 4, 2019

Interleukin (IL)-33 belongs to IL-1 cytokine family which is constitutively produced from the structural and lining cells including fibroblasts, endothelial cells, epithelial of skin, gastrointestinal tract, lungs that are exposed environment. Different most cytokines actively secreted nuclear IL-33 passively released during cell necrosis or when tissues damaged, suggesting it may function as an alarmin alerts immune system after damage infection, physical stress, trauma. plays important roles in type-2 innate immunity via activation allergic inflammation-related eosinophils, basophils, mast macrophages, group 2 lymphoid (ILC2s) through its receptor ST2. In this review, we focus on recent advances underlying intercellular intracellular mechanisms by can regulate inflammation various diseases asthma atopic dermatitis. The future pharmacological strategy application traditional Chinese medicines targeting IL-33/ST2 axis for anti-inflammatory therapy were also discussed.

Язык: Английский

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Luteolin as a modulator of skin aging and inflammation

BioFactors, Год журнала: 2020, Номер 47(2), С. 170 - 180

Опубликована: Дек. 25, 2020

Abstract Luteolin belongs to the group of flavonoids and can be found in flowers, herbs, vegetables spices. It plays an important role defending plants, for example against UV radiation by partially absorbing UVA UVB radiation. Thus, luteolin also decrease adverse photobiological effects skin acting as a first line defense. Furthermore, anti‐oxidative anti‐inflammatory activities were described on keratinocytes fibroblasts well several immune cells (e.g., macrophages, mast cell, neutrophils, dendritic T cells). suppress proinflammatory mediators IL‐1β, IL‐6, IL‐8, IL‐17, IL‐22, TNF‐α COX‐2) regulate various signaling pathway NF‐κB, JAK–STAT TLR pathway). In this way, modulates many inflammatory processes skin. The present review summarizes recent vitro vivo research field aging cancer, wound healing diseases, including psoriasis, contact dermatitis atopic dermatitis. conclusion, might promising molecule development topic formulations systemic agents diseases.

Язык: Английский

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Metabolic Pathways That Control Skin Homeostasis and Inflammation

Trends in Molecular Medicine, Год журнала: 2020, Номер 26(11), С. 975 - 986

Опубликована: Май 1, 2020

Keratinocytes and skin immune cells are actively metabolizing nutrients present in their microenvironment. This is particularly important common chronic inflammatory diseases such as psoriasis atopic dermatitis, characterized by hyperproliferation of keratinocytes expansion cells, thus suggesting increased cell nutritional requirements. Proliferating express high levels glucose transporter (GLUT)1, l-type amino acid (LAT)1, cationic transporters (CATs). Main metabolic regulators hypoxia-inducible factor (HIF)-1α, MYC, mechanistic target rapamycin (mTOR) control activation, proliferation, cytokine release. Here, we provide an updated perspective regarding the potential role nutrient pathways that could be to keratinocytes, dermatitis.

Язык: Английский

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Signaling pathways and targeted therapies for psoriasis

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Ноя. 27, 2023

Abstract Psoriasis is a common, chronic, and inflammatory skin disease with high burden on individuals, health systems, society worldwide. With the immunological pathologies pathogenesis of psoriasis becoming gradually revealed, therapeutic approaches for this have gained revolutionary progress. Nevertheless, mechanisms less common forms remain elusive. Furthermore, severe adverse effects recurrence upon treatment cessation should be noted addressed during treatment, which, however, has been rarely explored integration preliminary findings. Therefore, it crucial to comprehensive understanding behind pathogenesis, which might offer new insights research lead more substantive progress in expand clinical options treatment. In review, we looked briefly introduce epidemiology, subtypes, pathophysiology, comorbidities systematically discuss signaling pathways involving extracellular cytokines intracellular transmission, as well cross-talk between them. discussion, also paid attention potential metabolic epigenetic molecular mechanistic cascades related its comorbidities. This review outlined current psoriasis, especially targeted therapies novel strategies, mechanism recurrence.

Язык: Английский

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The PI3K-Akt-mTOR and Associated Signaling Pathways as Molecular Drivers of Immune-Mediated Inflammatory Skin Diseases: Update on Therapeutic Strategy Using Natural and Synthetic Compounds

Cells, Год журнала: 2023, Номер 12(12), С. 1671 - 1671

Опубликована: Июнь 20, 2023

The dysregulated phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway has been implicated in various immune-mediated inflammatory and hyperproliferative dermatoses such as acne, atopic dermatitis, alopecia, psoriasis, wounds, vitiligo, is associated with poor treatment outcomes. Improved comprehension the consequences PI3K/Akt/mTOR patients resulted development novel therapeutic approaches. Nonetheless, more studies are necessary to validate regulatory role this create effective preventive methods for a wide range skin diseases. Several have revealed that certain natural products synthetic compounds can obstruct expression/activity PI3K/Akt/mTOR, underscoring their potential managing common persistent disorders. This review summarizes recent advances understanding activated components discusses bioactive products, scaffolds, biologic agents prevention treatment. However, further research develop therapies

Язык: Английский

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The Immunology of Psoriasis—Current Concepts in Pathogenesis

Clinical Reviews in Allergy & Immunology, Год журнала: 2024, Номер 66(2), С. 164 - 191

Опубликована: Апрель 20, 2024

Abstract Psoriasis is one of the most common inflammatory skin diseases with a chronic, relapsing-remitting course. The last decades intense research uncovered pathological network interactions between immune cells and other types in pathogenesis psoriasis. Emerging evidence indicates that dendritic cells, T H 17 keratinocytes constitute pathogenic triad Dendritic produce TNF-α IL-23 to promote cell differentiation toward key psoriatic cytokines IL-17, IFN-γ, IL-22. Their activity results inflammation activation hyperproliferation keratinocytes. In addition, signaling pathways are implicated psoriasis, including 9 22 CD8 + cytotoxic neutrophils, γδ chemokines secreted by them. New insights from high-throughput analysis lesional identified novel populations involved pathogenesis. These studies not only expanded our knowledge about mechanisms response psoriasis but also resulted revolution clinical management patients Thus, understanding crucial for further studies, development therapeutic strategies, patients. aim review was comprehensively present dysregulation an emphasis on recent findings. Here, we described role B monocytes, mast innate lymphoid (ILCs), as well non-immune keratinocytes, fibroblasts, endothelial platelets initiation, development, progression

Язык: Английский

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Recent advances in our understanding of mast cell activation – or should it be mast cell mediator disorders?

Expert Review of Clinical Immunology, Год журнала: 2019, Номер 15(6), С. 639 - 656

Опубликована: Март 18, 2019

An increasing number of patients present with multiple symptoms affecting many organs including the brain due to mediators released by mast cells. These unique tissue immune cells are critical for allergic reactions triggered immunoglobulin E (IgE), but also stimulated (not activated) immune, drug, environmental, food, infectious, and stress triggers, leading secretion often without histamine tryptase. The presentation, diagnosis, management spectrum cell disorders very confusing. As a result, neuropsychiatric have been left out, diagnostic criteria made stricter excluding most patients. Areas covered: A literature search was performed on papers published between January 1990 November 2018 using MEDLINE. Terms used were activation, antihistamines, atopy, autism, fog, heparin, KIT mutation, IgE, inflammation, IL-6, IL-31, IL-37, luteolin, cells, mastocytosis, mediators, mycotoxins, release, secretion, tetramethoxyluteolin, Expert opinion: Conditions associated elevated serum or urine levels any mediator, in absence comorbidities that could explain levels, should be considered 'Mast Cell Mediator Disorders (MCMD).' Emphasis placed identification development drugs supplements inhibit their release.

Язык: Английский

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Epidermal mTORC1 Signaling Contributes to the Pathogenesis of Psoriasis and Could Serve as a Therapeutic Target

Frontiers in Immunology, Год журнала: 2018, Номер 9

Опубликована: Ноя. 30, 2018

Although modern biologics targeting different inflammatory mediators show promising therapeutic success, comprehensive knowledge about the molecular events in psoriatic keratinocytes that contribute to pathogenesis and could serve as targets is still scarce. However, recent efforts understand deregulated signal transduction pathways have led development of small molecule inhibitors e.g., tofacitinib Jak/Stat cascade opens additional options. Recently, PI3-K/Akt/mTOR signaling pathway has emerged an important player control epidermal homeostasis. This review summarizes current on role this psoriasis, especially manifestation disease discusses approaches target therapeutically.

Язык: Английский

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LncRNA MEG3 suppresses PI3K/AKT/mTOR signalling pathway to enhance autophagy and inhibit inflammation in TNF-α-treated keratinocytes and psoriatic mice

Cytokine, Год журнала: 2021, Номер 148, С. 155657 - 155657

Опубликована: Авг. 20, 2021

Язык: Английский

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Recent Updates on the Involvement of PI3K/AKT/mTOR Molecular Cascade in the Pathogenesis of Hyperproliferative Skin Disorders

Frontiers in Medicine, Год журнала: 2021, Номер 8

Опубликована: Апрель 30, 2021

PhosphoInositide-3 Kinase (PI3K) represents a family of different classes kinases which control multiple biological processes in mammalian cells, such as cell growth, proliferation, and survival. Class IA PI3Ks, the main regulators proliferative signals, consists catalytic subunit (α, β, δ) that binds p85 regulatory mediates activation AKT Target Of Rapamycin (mTOR) pathways regulation downstream effectors. Dysregulation PI3K/AKT/mTOR pathway skin contributes to several pathological conditions characterized by uncontrolled including cancers, psoriasis, atopic dermatitis (AD). Among cutaneous basal carcinoma (BCC) squamous (cSCC) display signaling hyperactivation, implicated hyperproliferation, tumorigenesis, well resistance apoptosis. Upregulation mTOR proteins has also been reported association with enhanced defective keratinocyte differentiation, senescence-like growth arrest, apoptosis, accounting for major parts overall disease phenotypes. On contrary, role AD is less characterized, even though recent evidence demonstrates relevant function epidermal barrier formation stratification. In this review, we provide most updates on molecular axis pathogenesis hyperproliferative disorders, highlights current status preclinical clinical studies PI3K-targeted therapies.

Язык: Английский

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