The Experts below are selected from a list of 69 Experts worldwide ranked by ideXlab platform
Richard P. Phipps - One of the best experts on this subject based on the ideXlab platform.
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Fibroblasts as Sentinel Cells. Synthesis of chemokines and regulation of inflammation.
The American journal of pathology, 1997Co-Authors: Roger S. Smith, Terry J. Smith, Timothy M. Blieden, Richard P. PhippsAbstract:In this commentary, we have suggested that the fibroblast should be considered a Sentinel Cell. This concept is based on the fibroblast's ability to function both as a structural element and as a vital immunoregulatory Cell. In some tissues, these capabilities may be ascribable to subsets of fibroblasts, rather than to some of the general fibroblast populations. The pioneering research of Xia et al, as well as that of others, highlights the need to explore the importance of fibroblasts as playing critical roles in disease. Emerging concepts regarding tissue-specific fibroblasts and fibroblast heterogeneity need to be considered in studies of their biosynthetic capabilities. Of special importance is the recent insight that the NF kappa B/RelB family of transcription proteins have apparently different regulatory roles in fibroblasts and hematopoietic Cells. Therefore, with regard to therapeutic strategies targeting molecules such as RelB, caution should be exercised as their interruption may have very different consequences in macrophages compared with fibroblasts. For example, inhibition of RelB in macrophages may well prevent enhanced chemokine expression, whereas in fibroblasts, a critical governor for preventing chemokine expression would be lost. Overall, this could lead to exacerbation of inflammation rather than to an attenuation of the process.
Julian R. Naglik - One of the best experts on this subject based on the ideXlab platform.
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Analysis of Epithelial Cell Responses to Microbial Pathogens
Methods in molecular biology (Clifton N.J.), 2021Co-Authors: Spyridoula Angeliki Nikou, Olivia W. Hepworth, Nicole O. Ponde, Ruth E. Dickenson, Jonathan P. Richardson, Julian R. NaglikAbstract:The epithelial Cell is usually the first host Cell that interacts with the microbiota present at mucosal surfaces. Although initially thought of as "bystander" Cells with barrier function, the epithelial Cell is now known to be a Sentinel Cell in the recognition and discrimination of commensal and pathogenic microorganisms and a key Cell in initiating subsequent innate and adaptive immune responses. Here, we describe the main assays utilized in analyzing the activation of epithelial Cell signaling (western blotting), transcription factors (TransAm), gene expression (quantitative reverse transcription PCR (qRT-PCR)), cytokine responses (ELISA, Luminex), and damage induction (lactate dehydrogenase (LDH) release). While our laboratory focuses on the epithelial response to Candida pathogens, these assays can be applied universally to analyze the activation of epithelial Cells in response to any microbial pathogen.
Roger S. Smith - One of the best experts on this subject based on the ideXlab platform.
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Fibroblasts as Sentinel Cells. Synthesis of chemokines and regulation of inflammation.
The American journal of pathology, 1997Co-Authors: Roger S. Smith, Terry J. Smith, Timothy M. Blieden, Richard P. PhippsAbstract:In this commentary, we have suggested that the fibroblast should be considered a Sentinel Cell. This concept is based on the fibroblast's ability to function both as a structural element and as a vital immunoregulatory Cell. In some tissues, these capabilities may be ascribable to subsets of fibroblasts, rather than to some of the general fibroblast populations. The pioneering research of Xia et al, as well as that of others, highlights the need to explore the importance of fibroblasts as playing critical roles in disease. Emerging concepts regarding tissue-specific fibroblasts and fibroblast heterogeneity need to be considered in studies of their biosynthetic capabilities. Of special importance is the recent insight that the NF kappa B/RelB family of transcription proteins have apparently different regulatory roles in fibroblasts and hematopoietic Cells. Therefore, with regard to therapeutic strategies targeting molecules such as RelB, caution should be exercised as their interruption may have very different consequences in macrophages compared with fibroblasts. For example, inhibition of RelB in macrophages may well prevent enhanced chemokine expression, whereas in fibroblasts, a critical governor for preventing chemokine expression would be lost. Overall, this could lead to exacerbation of inflammation rather than to an attenuation of the process.
Michael G Brown - One of the best experts on this subject based on the ideXlab platform.
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rna sensors enable human mast Cell anti viral chemokine production and ifn mediated protection in response to antibody enhanced dengue virus infection
PLOS ONE, 2012Co-Authors: Michael G Brown, Sarah M Mcalpine, Yan Y Huang, Ian D Haidl, Ayham Alafif, Jean S Marshall, Robert AndersonAbstract:Dengue hemorrhagic fever and/or dengue shock syndrome represent the most serious pathophysiological manifestations of human dengue virus infection. Despite intensive research, the mechanisms and important Cellular players that contribute to dengue disease are unclear. Mast Cells are tissue-resident innate immune Cells that play a Sentinel Cell role in host protection against infectious agents via pathogen-recognition receptors by producing potent mediators that modulate inflammation, Cell recruitment and normal vascular homeostasis. Most importantly, mast Cells are susceptible to antibody-enhanced dengue virus infection and respond with selective cytokine and chemokine responses. In order to obtain a global view of dengue virus-induced gene regulation in mast Cells, primary human cord blood-derived mast Cells (CBMCs) and the KU812 and HMC-1 mast Cell lines were infected with dengue virus in the presence of dengue-immune sera and their responses were evaluated at the mRNA and protein levels. Mast Cells responded to antibody-enhanced dengue virus infection or polyinosiniċpolycytidylic acid treatment with the production of type I interferons and the rapid and potent production of chemokines including CCL4, CCL5 and CXCL10. Multiple interferon-stimulated genes were also upregulated as well as mRNA and protein for the RNA sensors PKR, RIG-I and MDA5. Dengue virus-induced chemokine production by KU812 Cells was significantly modulated by siRNA knockdown of RIG-I and PKR, in a negative and positive manner, respectively. Pretreatment of fresh KU812 Cells with supernatants from dengue virus-infected mast Cells provided protection from subsequent infection with dengue virus in a type I interferon-dependent manner. These findings support a role for tissue-resident mast Cells in the early detection of antibody-enhanced dengue virus infection via RNA sensors, the protection of neighbouring Cells through interferon production and the potential recruitment of leukocytes via chemokine production.
David E. Cochrane - One of the best experts on this subject based on the ideXlab platform.
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Peptide regulation of mast-Cell function.
Progress in Medicinal Chemistry, 2008Co-Authors: David E. CochraneAbstract:Publisher Summary This chapter discusses the peptide regulation of mast-Cell function. The ability of peptides of immune, neural, and endocrine origin to affect mast-Cell function is now well established. Once viewed with only passing pharmacological interest and believed to be of little physiological relevance, peptides are now recognized as important regulators of mast-Cell secretion, growth, and development. Besides, they are now believed to participate with mast Cells in allergic disease, in bronchial asthma, and in various states of inflammation. The ability of peptides to modulate mast-Cell function could contribute to the suggested roles for mast Cells in the control of the microenvironment and in tissue growth and repair. Mast Cells have been studied because of their prominent role in the reactions of immediate-type hypersensitivity. A widely distributed fixed tissue Cell, the mast Cell, is particularly prevalent in organs with a high percentage of connective tissue and is most numerous in the skin and in the linings of the respiratory, gastrointestinal, and reproductive tracts, tissues that interface with the external environment. In these various locations, mast Cells are frequently found in close proximity to small blood vessels and nerves. This prominence of the mast Cell in tissues that interface with the external world is strategic to its role as the Sentinel Cell of the inflammatory response.
