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Cytokine-Binding Proteins
Published in Jason Kelley, Cytokines of the Lung, 2022
James C. Bonner, Arnold R. Brody
The secretion of several different cytokines by various pulmonary effector cells influences the proliferation, chemotaxis, and extracellular matrix production by target cells in the lung, such as fibroblasts (Kelley, 1990). Defining the complex control of these cytokine-mediated cellular responses under normal and pathological conditions will be essential toward developing a therapeutic regimen aimed at preventing aberrant expression of cytokines or their receptors. Such activity has been implicated in several lung diseases, including pulmonary fibrosis, sarcoidosis, pneumoconioses, scleroderma, and hyperoxia (reviewed in Kelley, 1990). Most of these cytokines are regulated extracellularly by one or more binding proteins that modify the cytokine-mediated target cell responsiveness. Thus, a complete characterization of these cytokine–CBP interactions and the elucidation of the mechanisms by which these CBPs modulate cytokine action could be key to understanding the cell–cell interactions involved in fibrogenesis and carcinogenesis. Additionally, levels of CBPs and cytokines from bronchoalveolar lavage (BAL) fluid and conditioned medium from lavaged macrophages could be useful biological markers in characterizing cytokine–CBP profiles in humans during various stages of lung disease. These measurements could be particularly useful in cases where cytokines and CBPs are up-regulated, since pathological conditions, such as pulmonary fibrosis, have been associated with increased levels of certain cytokines.
Soluble Mediators of Cellular Cooperation: The Cytokines
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
A failure of cytokine gene transcription may also be responsible for some cases of severe combined immunodeficiency. Figure 7–1 is a diagram of the promoter region of the IL-2 gene. It has organization and sequence elements similar to those of promoters and enhancers of immunoglobulin and T cell receptor genes (see Chapters 4 and 6). In some cases of SCID, patients appear to have a defect in production of IL-2 and/or other cytokines which is not related to actual lesions in the genes encoding them. These conditions may result from abnormal transcriptional regulation of cytokine synthesis. One patient has been described in which the NFAT-1 transcription factor appeared to be abnormal.
Eosinophil-Active Cytokines in Human Disease: Development and Use of Monoclonal Antibodies to IL-3, IL-5, and GM-CSF
Published in Gerald J. Gleich, A. Barry Kay, Eosinophils in Allergy and Inflammation, 2019
John S. Abrams, Jon E. Silver, Robert E. Van Dyke, Gerald J. Gleich
Clinical conditions associated with eosinophilia and the presence of eosinophilactive cytokines, primarily IL-5, have been identified. Eosinophilia can result from a diverse set of etiologies with differing underlying mechanisms. IL-5 can be consistently observed in a variety of eosinophilic conditions such as IL-2-associated eosinophilia, the Mazzotti reaction, and episodic angioedema, which represent the high-end levels of circulating IL-5. Hypereosinophilic syndrome and certain types of asthmas may represent the low end, where barely detectable levels of circulating IL-5 are present, yet these levels are sufficient to maintain the hypereosinophilic state. One principal issue is whether low levels of IL-5 or other eosinophil-active cytokines are present in a particular compartment and, although not in general circulation, are potentially locally active. To answer this question, detection methodologies must shift from analyses of bulk fluids to the specific detection of cytokines within microenvironments or single cells in tissue. We are currently developing immunohistochemical methodology to carry out these analyses. The availability of such methods will be a key step in furthering understanding of the role of cytokines in disease.
Effects of Complement Regulators and Chemokine Receptors in Type 2 Diabetes
Published in Immunological Investigations, 2021
B Aydin Ozgur, E Coskunpinar, S Bilgic Gazioglu, A Yilmaz, Y Musteri Oltulu, B Cakmakoglu, G Deniz, AO Gurol, MT Yilmaz
Cytokines are also known to have a role in pathogenesis of many immune-mediated diseases. They enable migration of leukocytes to sites of inflammation where these latter cells can differentiate or become activated (Ratajczak et al. 2003). SDF-1, which belongs to CXC chemokine family, is a small chemotactic cytokine that is expressed in various organs and is known to be involved in many biological processes (De Oliveire et al. 2011). SDF-1 and its receptor CXCR-4 together play an important role in many normal and pathologic processes, including immunologic homeostasis, hematopoiesis and embryogenesis (Lee et al., 2011a; 2011b). Polymorphisms in SDF-1 and CXCR-4 genes have effects on inflammatory disease and provide predisposition that has been shown by relative studies (Barcellos et al. 2000).
Lung damage by thoron progenies versus possible damage redemption by lung stem cells: a perspective
Published in International Journal of Radiation Biology, 2020
Debajit Chaudhury, Utsav Sen, Nagesh N. Bhat, Bijay Kumar Sahoo, Sudheer Shenoy P, Bipasha Bose
Ionizing radiations are responsible for the mitotic catastrophe that causes hyper-amplification and over duplication of chromosomes, resulting in micronuclei formation (Seideman et al. 2011). In the lung somatic and stem cells following thoron inhalation, the status of the cell cycle checkpoint proteins, DNA strand breaks, concerning thoron dosages will comprise an important aspect of the mechanistic studies. Cells that escape mitotic arrest often fail cytokinesis, resulting in tetraploid DNA content and abnormal nuclei forming giant cells thereby leading to cancer initiation (Vogel et al. 2007). Recent studies have also suggested the ionizing radiation-induced necroptosis (programmed necrosis) through the engagement of ligand-DR (Death receptor) under the conditions where the apoptotic pathway is either blocked or deficient (Degterev and Yuan 2008). Here, in context with thoron inhalation, the decay of thoron progenies leads to the emission of radiation that might be involved in necroptosis and is worth investigating.
Multiomic analysis of cytokines in immuno-oncology
Published in Expert Review of Proteomics, 2020
With the development of new techniques in immunology, chemistry, physics, molecular biology, gene technology, and the ability to manufacture recombinant human cytokines, this has given us the possibility of measuring cytokines in a variety of cellular fluids and diverse tissues. The choice of which method to use to determine a cytokine is not simple, and depends on the goal of the research and at what cellular level it is necessary to conduct the test. Deregulation of cytokine gene expression and cytokine values are well documented in many cancer patients [22], but the timing of cytokine synthesis in the cell, due to the transit effect, is of great importance during method selection [9,25,27]. At the same time, the possibility of neutralizing or activating another protein might guide the choice of method for determining the cytokine (Figure 2). Despite the recent introduction of new methods with potentially wide applications, and despite the great specificity for fundamental research, it is still recommended to use several rather than one single method. At least two validated methods were previously recommended to accurately confirm and standardize results [48].