Molecular Characterization of Human Airway Epithelium Innate Immunity by IL-17 Regulation PDF Download

Author: Cheng-Yuan Kao
Publisher:
ISBN:
Category :
Languages : en
Pages : 378

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Author: Sharlene Velichko
Publisher:
ISBN: 9781124908731
Category :
Languages : en
Pages :

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The role of the proinflammatory cytokine interleukin-17 (IL-17) in the airway has been under investigation for the last 12 years. Many studies have been published demonstrating its pleiotropic role in the production of chemokines, cytokines, mucins, and antimicrobial proteins. Many in vivo models have demonstrated the association of IL-17 in airway inflammation in response to allergens as well as environmental insults, as well as chronic inflammatory lung diseases such as cystic fibrosis, chronic obstructive pulmonary disease and asthma. However, relatively little is known regarding the downstream signaling mechanisms by which IL-17 mediates its many effects. What is known is that the signaling is complex; IL-17 has been shown to involve multiple signaling pathways, including: the canonical NF-kappaB pathway, multiple mitogen-activated protein (MAP) kinase pathways, as well as C/EBP, PI-3 kinase and JAK. Both cell type and target gene appear to determine the signaling pathway involved downstream of IL-17. Little is known regarding the protein-protein interactions that mediate these signaling events. What is known is that the intracellular protein Act1 (also known as CIKS) is an important downstream mediator of IL-17 induced signaling. Cells derived from Act1-deficient mice are largely unresponsive to IL-17A stimulation. Act1 has been shown to contain both TRAF6 and IL-17 receptor binding sites, and therefore acts as an intermediate to connect the activated IL-17 receptor complex to pathways downstream of TRAF6. However, Act1 has additional functions as well. It can also bind to the IL-25, CD40 and BAFF-R receptors, and has recently been shown to act as a U-box type E3 ubiquitin ligase. Recently, a single nucleotide polymorphism (SNP) that encodes a loss-of-function mutation in the gene for Act1, TRAF3IP2, was associated with psoriasis, an autoimmune inflammatory skin disease, and psoriatic arthritis. As IL-17 is associated with the pathogenesis of psoriasis, this is counter-intuitive to the known functions of Act1, indicating that Act1 may have other functions as well. This dissertation details a novel nuclear function for Act1 as a transcriptional enhancer. Subsequent RNA-seq comparison of cells ectopically expressing Act1 and IL-17A stimulated cells identified a number of cornified envelope constituents whose expression is up-regulated by both Act1 and IL-17. The cornified envelope is a structure formed in the outermost layer of stratified squamous epithelia. Finally, we detail the use of a yeast two hybrid assay to identify novel Act1 interacting proteins, and further characterize the interaction of Act1 with one of these proteins, COMMD1 (copper metabolism (Murr1) domain containing 1), which might represent a new target of Act1's ubiquitin ligase activity.

Author: Fei Huang
Publisher:
ISBN:
Category :
Languages : en
Pages : 226

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Author:
Publisher:
ISBN:
Category : Dissertations, Academic
Languages : en
Pages : 942

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Author: Steven L. Kunkel
Publisher: Marcel Dekker
ISBN:
Category : Medical
Languages : en
Pages : 592

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A comprehensive text providing much of the currently available knowledge in the field of cytokines. There are four areas covered, including general overviews of each of the major cytokines, listings of the important interactions these cytokines have with inflammatory cells, discussions of current an

Author: Peter Howarth
Publisher: CRC Press
ISBN: 9780429132582
Category : MEDICAL
Languages : en
Pages : 328

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This landmark volume discusses the characteristics and impact of the remodeling process on airway function and clinical disease expression within the airway in asthma, covering pharmacological therapies and possible future targets relevant to regulating the remodeling process. Emphasizes the importance of treating underlying airway inflammation and the relevance of structural alterations to the airway wall, including glandular increases, enhanced collagen deposition within the submucosa, increased vasculature, smooth hypertrophy, and hyperplasias! Tracing the development and maintenance of bronchial hyperresponsiveness, decline in lung function, and loss of reversibility evident in chronic asthma, Airway Remodelingdescribes the contribution of inflammatory cells in the development of airway structural changes examines how pharmaceutical agents act and whether existing treatments modify or prevent remodeling in chronically inflamed asthmatic airways considers whether neural pathways initiate as well as contribute to the airway inflammatory cascade that leads to remodeling reviews the action of cytokines and growth factors on ASM signaling outlines novel approaches to regulating smooth muscle growth clarifies whether permanent ventilatory incapacity in asthma is caused by the uncoupling of the airway and the role of the lung parenchyma details high-resolution computerized tomography scan to measure the internal size of the airway at baseline, during challenge, or after bronchodilatation and more!Improving lung function and quality of life by reducing the need for emergency care, hospital admissions, and systemic steroid administration, Airway Remodeling is a superb reference for pulmonologists and respiratory system specialists; physiologists; pneumologists; allergists; pharmacologists; molecular, cellular, and lung biologists; and graduate and medical school students in these disciplines.

Author: R. Lee Reinhardt
Publisher: Humana
ISBN: 9781493978953
Category : Medical
Languages : en
Pages : 0

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This book provides researchers the opportunity to investigate type-2-associated diseases in their laboratories. Beginning with chapters describing various models of type-2 immunity, the volume then continues by detailing cellular protocols designed to identify, characterize, and assess the function of key adaptive and innate immune cells involved in type-2 inflammation; approaches to isolate and evaluate specific cellular subsets at the genetic, epigenetic, and molecular level; protocols to assess type-2 immunity and its relationship to organismal and metabolic systems (ex. Microbiome). This book concludes with a section that explores the use of primary human cells in evaluating relevance to the clinic. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Vital and authoritative, Type 2 Immunity: Methods and Protocols aims to provide a broad network of methods that can be used to develop a hypothesis and investigate its potential from bench to beside.

Author: Joanna Picot
Publisher: Springer Science & Business Media
ISBN: 1592598617
Category : Science
Languages : en
Pages : 357

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A thoroughly revised and updated collection readily reproducible techniques for culturing human cells. This new edition includes a wide range of human cell types relevant to human disease and new chapters on fibroblasts, Schwann cells, gastric and colonic epithelial cells, and parathyroid cells. The protocols follow the successful Methods in Molecular MedicineTM series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.

Author: Z. Kmiec
Publisher: Springer Science & Business Media
ISBN: 3642565530
Category : Science
Languages : en
Pages : 154

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It is only during the last decade that the functions of sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, pit cells and other intrahepatic lymphocytes have been better understood. The development of methods for isolation and co-culturing various types of liver cells has established that they communicate and cooperate via secretion of various intercellular mediators. This monograph summarizes multiple data that suggest the important role of cellular cross-talk for the functions of both normal and diseased liver. Special features of the book include concise presentation of the majority of detailed data in 19 tables. Original schemes allow for the clear illustration of complicated intercellular relationships. This is the first ever presentation of the newly emerging field of liver biology, which is important for hepatic function in health and disease and opens new avenues for therapeutic interventions.

Author: Scott H. Randell
Publisher: Humana Press
ISBN: 9781493956791
Category : Science
Languages : en
Pages : 469

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Fascinating biology occurs at epithelial interfaces, whether between organism and environment or within body compartments, and many diseases inflicting huge personal and societal burdens result from dysfunction of epithelial systems, e.g., carcinomas. Epithelial cell cultures have been an integral and crucial part of the biomedical research enterprise, adding unique capabilities and enabling mechanistic approaches. In the past decade there have been many research advances, such as directed differentiation of embryonic stem cells and induced pluripotent stem cells, robotic high throughput screening, whole genome siRNA and shRNA libraries, massively parallel sequencing at low cost, identification of somatic stem cells in key organs, to name a few. Epithelial Cell Culture Protocols, Second Edition provides a cross section of up-to-date culture protocols for the most heavily studied cell systems and featured supporting technologies. Written in the successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Epithelial Cell Culture Protocols, Second Edition will serve outstanding investigators with the best possible information for the advancement of biomedical science.