Targeting cell signaling in allergic asthma

Signal Transduction and Targeted Therapy, Год журнала: 2019, Номер 4(1)

Опубликована: Окт. 17, 2019

Asthma is chronic inflammation of the airways characterized by airway hyper-responsiveness, wheezing, cough, and dyspnea. affects >350 million people worldwide. The Th2 immune response a major contributor to pathophysiology asthma. Targeted therapy modulating cell signaling pathways can be powerful strategy design new drugs treat potential molecular that targeted include IL-4-IL-13-JAK-STAT-MAP kinases, adiponectin-iNOS-NF-κB, PGD2-CRTH2, IFNs-RIG, Wnt/β-catenin-FAM13A, FOXC1-miR-PI3K/AKT, JNK-Gal-7, Nrf2-ROS, Foxp3-RORγt, CysLTR, AMP, Fas-FasL, PTHrP/PPARγ, PAI-1, FcɛRI-LAT-SLP-76, Tim-3-Gal-9, TLRs-MyD88, PAR2, Keap1/Nrf2/ARE. Therapeutic designed target one or more these

Язык: Английский

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Selective JAKinibs: Prospects in Inflammatory and Autoimmune Diseases

BioDrugs, Год журнала: 2019, Номер 33(1), С. 15 - 32

Опубликована: Янв. 30, 2019

Cytokines, many of which signal through the JAK-STAT (Janus kinase-Signal Transducers and Activators Transcription) pathway, play a central role in pathogenesis inflammatory autoimmune diseases. Currently three JAK inhibitors have been approved for clinical use USA and/or Europe: tofacitinib rheumatoid arthritis, psoriatic arthritis ulcerative colitis, baricitinib ruxolitinib myeloproliferative neoplasms. The target multiple JAKs at high potency current research has focused on more selective inhibitors, almost dozen currently are being evaluated trials. In this narrative review, we summarize status pan-JAK or trials, discuss rationale targeting

Язык: Английский

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Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis

JAMA Dermatology, Год журнала: 2020, Номер 156(12), С. 1333 - 1333

Опубликована: Сен. 30, 2020

Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced disease severity in moderate to severe atopic dermatitis (AD) phase 3 monotherapy studies.

Язык: Английский

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Racial differences in atopic dermatitis

Annals of Allergy Asthma & Immunology, Год журнала: 2018, Номер 122(5), С. 449 - 455

Опубликована: Ноя. 20, 2018

Язык: Английский

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Targeting the Janus Kinase Family in Autoimmune Skin Diseases

Frontiers in Immunology, Год журнала: 2019, Номер 10

Опубликована: Окт. 9, 2019

Autoimmune skin diseases are characterized by significant local and systemic inflammation that is largely mediated the Janus kinase (JAK)-signal transducer activator of transcription (STAT) pathway. Advanced understanding this pathway has led to development targeted inhibitors kinases (JAKinibs). As a class, JAK effectively treat multitude hematologic inflammatory diseases. Growing evidence suggests efficacious in atopic dermatitis, alopecia areata, psoriasis, vitiligo. Additional inhibition might be broadly useful dermatology, with early reports efficacy several other conditions. can administered orally or used topically represent promising new class medications. Here we review evolving data on role JAK-STAT dermatoses potential therapeutic benefit antagonism.

Язык: Английский

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Pathogenesis of allergic diseases and implications for therapeutic interventions

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

Опубликована: Март 24, 2023

Abstract Allergic diseases such as allergic rhinitis (AR), asthma (AAS), atopic dermatitis (AD), food allergy (FA), and eczema are systemic caused by an impaired immune system. Accompanied high recurrence rates, the steadily rising incidence rates of these attracting increasing attention. The pathogenesis is complex involves many factors, including maternal-fetal environment, living genetics, epigenetics, body’s status. exhibits a marked heterogeneity, with phenotype endotype defining visible features associated molecular mechanisms, respectively. With rapid development immunology, biology, biotechnology, new biological drugs have been designed for treatment diseases, anti-immunoglobulin E (IgE), anti-interleukin (IL)-5, anti-thymic stromal lymphopoietin (TSLP)/IL-4, to control symptoms. For doctors scientists, it becoming more important understand influencing pathogenesis, progress diseases. This review aimed assess epidemiology, therapeutic interventions AR, AAS, AD, FA. We hope help scientists systematically.

Язык: Английский

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JAK–STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Дек. 8, 2022

Atopic dermatitis (AD) is a chronic, inflammatory, pruritic form of dermatosis with heterogeneous manifestations that can substantially affect patients' quality life. AD has complex pathogenesis, making treatment challenging for dermatologists. The Janus kinase (JAK)–signal transducer and activator transcription (STAT) pathway plays central role in modulating multiple immune axes involved the immunopathogenesis AD. In particular, Th2 cytokines, including interleukin (IL)-4, IL-5, IL-13, IL-31, thymic stromal lymphopoietin, which contribute to symptoms chronic inflammation pruritus AD, are mediated by JAK–STAT signal transduction. Furthermore, regulation epidermal barrier modulation peripheral nerves related transduction pruritus. Targeting may attenuate these signals show clinical efficacy through suppression various pathways associated Topical oral JAK inhibitors variable selectivity have emerged as promising therapeutic options Notably, topical ruxolitinib, upadacitinib, abrocitinib were approved U.S. Food Drug Administration treating patients Accordingly, present study reviewed pathogenesis explored updated applications

Язык: Английский

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Expert consensus on the systemic treatment of atopic dermatitis in special populations

Journal of the European Academy of Dermatology and Venereology, Год журнала: 2023, Номер 37(6), С. 1135 - 1148

Опубликована: Янв. 25, 2023

Abstract With the increasing number of options for treatment moderate‐to‐severe atopic dermatitis, clinicians need guidance on a practical approach to selecting systemic agent specific patient populations. We convened an expert panel consisting 12 members conduct literature review and summarize relevant data related six scenarios clinical interest: comorbid asthma, ocular surface disease, history cancer, past ongoing infections interest (including herpes simplex virus, zoster, hepatitis B, tuberculosis), pregnancy lactation, elderly. performed search examined each scenario with respect three major categories available agents: traditional systemics (azathioprine, cyclosporine A, methotrexate, mycophenolate mofetil), Janus kinase inhibitors (abrocitinib, baricitinib, upadacitinib), biologics (dupilumab, lebrikizumab, tralokinumab). The steering committee met virtually discuss drafted consensus statements. A modified Delphi process was used arrive at set final statements AD in these To provide choice therapy dermatitis topics interest, 25 summary supporting are presented herein.

Язык: Английский

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Contribution of STAT3 to Inflammatory and Fibrotic Diseases and Prospects for its Targeting for Treatment

International Journal of Molecular Sciences, Год журнала: 2018, Номер 19(8), С. 2299 - 2299

Опубликована: Авг. 5, 2018

Signal transducer and activator of transcription (STAT) 3 plays a central role in the host response to injury. It is activated rapidly within cells by many cytokines, most notably those IL-6 family, leading pro-proliferative pro-survival programs that assist regaining homeostasis. With persistent activation, however, chronic inflammation fibrosis ensue, number debilitating diseases. This review summarizes advances our understanding STAT3 its targeting diseases marked and/or with focus on largest unmet medical need.

Язык: Английский

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New treatments for atopic dermatitis targeting beyond IL-4/IL-13 cytokines

Annals of Allergy Asthma & Immunology, Год журнала: 2019, Номер 124(1), С. 28 - 35

Опубликована: Окт. 14, 2019

Язык: Английский

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