Transcriptional Regulation Of Macrophage Function
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Transcriptional Regulation Of Macrophage Function
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Author : Marten A. Hoeksema
language : en
Publisher: Frontiers Media SA
Release Date : 2023-12-26
Transcriptional Regulation Of Macrophage Function written by Marten A. Hoeksema and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2023-12-26 with Medical categories.
Rev Erb In Macrophage Gene Expression
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Author : Michael Tun Yin Lam
language : en
Publisher:
Release Date : 2011
Rev Erb In Macrophage Gene Expression written by Michael Tun Yin Lam and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with categories.
This dissertation contains four divisions represented in three chapters. The first chapter introduces transcription factor Rev-Erb, a transcriptional repressor belonging to the superfamily of nuclear receptors. Chapter 1 then continues with the physiological roles and functional mechanisms of enhancers. These are DNA regulatory elements key to orchestrate temporal and spatial expression of genes. Our work on Rev-Erb in macrophages, described in the second chapter, provides evidences of a novel transcription regulatory mechanism at enhancer elements. We identified novel target genes of Rev-Erb, such as matrix metalloproteases 9 (mmp9) and fractalkine receptor (Cx3cr1), which are negatively regulated by Rev-Erb from distal enhancer elements. In fact, genome-wide binding analysis shows that most Rev-Erb localizes to putative macrophage enhancers. A recent discovery demonstrated that RNAs are actively transcribed at enhancers on a genomic-scale. In line with this finding, Rev-Erb represses RNA transcription at enhancers. The mechanism is similar to its action at promoters by inhibition of RNA polymerase II recruitment and deacetylation of histones. Given that both enhancer-RNAs (eRNAs) and mRNAs are negatively regulated by Rev-Erb, we further test whether eRNA is a functional intermediate for target gene regulation. Using Mmp9 as a model, targeting its eRNA with RNA interference decreases mRNA expression. Furthermore, in Rev-Erb deficient macrophages, both Mmp9 eRNA and mRNA are derepressed; but targeting eRNA is sufficient to reverse Mmp9 mRNA derepression. Our finding suggests a functional role for enhancer-RNA. When acting through enhancers, Rev-Erb regulates target genes by repressing transcription at enhancers as a mechanistic intermediate. The last chapter explores ways to utilize the enormousness of genome-scale data from human populations to study functions of transcription regulatory elements relevant to diseases through forward genetics. Understanding mechanisms of transcriptional regulation, including discoveries of functional and targetable intermediates such as enhancer-RNAs, suggests new methods of disease detection and treatment.
Transcriptional And Translational Regulation Of Macrophage Activation By Interferon Gamma
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Author : Xiaodi Su
language : en
Publisher:
Release Date : 2014
Transcriptional And Translational Regulation Of Macrophage Activation By Interferon Gamma written by Xiaodi Su and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014 with categories.
Interferon-gamma (IFN-[gamma]) is a key activating cytokine for macrophages, and it also functions to regulate macrophage responses to other cytokines and inflammatory factors. Here we explored the mechanisms by which IFN-[gamma] regulates immunoreceptor tyrosine based activation motif (ITAM) signaling in primary macrophages. Ligation of ITAM-coupled receptors induces a group of negative regulators of inflammation, including IL-I0, SOCS3, ABIN3 and A20, which function cooperatively to dampen TLR response. We found that IFN-[gamma] strongly inhibited the induction of these negative regulators by ITAM signaling, and identified glycogen synthase kinases 3 (GSK3) as the major mediator. Specifically, IFN-[gamma] increased GSK3 activity and regulated its cellular distribution. IFN-[gamma] also suppressed AP-1 and CREB, transcription factors important for IL-10 expression and negatively regulated by GSK3. These findings provide a novel mechanism for crosstalk between IFN-[gamma] and ITAM signaling and highlight a critical role for GSK3 in mediating immunoregulatory effects of IFN-[gamma]. IFN-[gamma]-mediated control over gene transcription has been extensively studied, but little is known about whether IFN-[gamma] directly affects protein translation and cellular metabolism in macrophages. We demonstrated that IFN-[gamma] suppressed the inflammatory gene regulator HES 1 at the level of translation. IFN-[gamma] inhibited two essential pathways that promote protein synthesis, MNK-eIF4E and mTORC1. The central integrator of nutrient sensing and cellular metabolism is mTORC1. IFN-[gamma] suppressed M-CSFR expression, and attenuated PI3K-Akt signaling that is required for mTORC 1 activation. Additionally, IFN-[gamma] depleted intracellular tryptophan and suppressed mTOR recruitment to lysosomal membrane, where mTOR can be activated. Disruption of the activating signals from growth factor and amino acids by IFN-[gamma] led to mTORC1 inactivation and translation inhibition. To identify the mRNA targets of IFN-[gamma]-mediated translational regulation, we performed genome-wide ribosome profiling, a method for direct measurement of protein translation. Ribosome profiling revealed several hundred genes, including cytokines, cheinokines and metabolite transporters, were regulated at the translational level by IFN-[gamma]. Our studies uncover a novel pathway by which IFN-[gamma] suppresses phosphorylation of eIF4E and metabolism checkpoint kinase mTOR to inhibit protein translation. These results provide insights in the underappreciated role of IFN-[gamma] in translational regulation and metabolism reprogramming of macrophages.
Macrophage Regulation Of Immunity
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Author : Emil Unanue
language : en
Publisher: Elsevier
Release Date : 2012-12-02
Macrophage Regulation Of Immunity written by Emil Unanue and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-02 with Science categories.
Macrophage Regulation of Immunity contains the proceedings of a conference held in Augusta, Michigan, on March 12-14, 1979. The papers examine the role of macrophages in the regulation of cellular immune reactions. They highlight the interaction between macrophages and T cells, along with immune response gene control and macrophage secretion of a number of lymphostimulatory molecules. Organized into six sections encompassing 35 chapters, this volume begins with an overview of antigen handling and presentation, immune response gene control, antigen-presenting cells, and factors affecting lymphocyte-macrophage interactions. It then discusses genetic control of T cell-macrophage interaction in helper cell induction in vitro; mechanisms underlying the interaction of guinea pig T lymphocytes with antigen-pulsed macrophages; and secretion of arachidonic acid oxygenation products by mononuclear phagocytes and their possible role as modulators of lymphocyte function. The book also covers regulation of intracellular killing by extracellular stimulation of the monocyte membrane, and adjuvant activation of macrophage functions. Students and scientists will find this book extremely helpful.
Chromatin And Transcriptional Regulation In Mouse Macrophages
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Author : Michael McAndrew
language : en
Publisher:
Release Date : 2017
Chromatin And Transcriptional Regulation In Mouse Macrophages written by Michael McAndrew and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017 with Electronic dissertations categories.
The Role Of Trem2 In Myocardial Injury And Transcriptional Regulation Of Macrophage Phenotypes
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Author : Thomas Andreas Prohaska
language : en
Publisher:
Release Date : 2022
The Role Of Trem2 In Myocardial Injury And Transcriptional Regulation Of Macrophage Phenotypes written by Thomas Andreas Prohaska and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022 with categories.
TREM2 (Triggering Receptor Expressed on Myeloid Cells 2) is a transmembrane receptor that has recently been established as a key regulator of macrophages in multiple disease models. It is highly expressed in distinct macrophage populations in models of Alzheimer's Disease, non-alcoholic steatohepatitis, and obesity. In this study, we interrogated the effect of deletion of TREM2 or treatment with a TREM2-activating antibody in myocardial injury models. To understand how TREM2 itself is regulated and how it mediates its effects on transcription, we established a conditionally immortalized monocyte progenitor cell line that constitutively expresses Cas9 and is able to differentiate into macrophages. We used this cell line to delete the intergenic enhancer of TREM2 and to knock out TREM2 as well as transcription factors. Thereby, we identified transcription factors mediating the effects of TREM2 on gene expression. Overall, in this work we demonstrate the role of TREM2 in myocardial injury, interrogate regulation of Trem2 expression, and identify transcription factors downstream of TREM2 signaling.
Transcriptional Control Points During Macrophage Development That Influence The Macrophage Activation Response
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Author : Mary Ann McDowell
language : en
Publisher:
Release Date : 1995
Transcriptional Control Points During Macrophage Development That Influence The Macrophage Activation Response written by Mary Ann McDowell and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1995 with categories.
Transcriptional Control Of Macrophage Function In The Pig And Its Relationship To Infectious Disease Susceptibility
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Author : Lynsey Fairbairn
language : en
Publisher:
Release Date : 2012
Transcriptional Control Of Macrophage Function In The Pig And Its Relationship To Infectious Disease Susceptibility written by Lynsey Fairbairn and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012 with categories.
The biology of cells of the mononuclear phagocyte system has been studied extensively in the mouse. Studies of the pig as an experimental model have commonly been consigned to specialist animal science journals. This thesis considered some of the many ways that pigs may address the shortcomings of mice as models for the study of macrophage differentiation and activation in vitro, and the biology of sepsis and other pathologies in the living animal. Flow cytometry was used initially to phenotype cells from the porcine lung, peritoneal cavity, blood and bone marrow using the LPS receptor CD14 and the FC receptor CD16, markers frequently employed to differentiate human monocytes into subsets. The expression of SIRP-alpha (SWC3a, CD172a), which is present on all cells of myeloid origin, and the haemoglobin scavenger receptor, CD163 which has previously been used to study monocyte differentiation in the pig was also studied. The findings validated previous work where blood monocytes were divided into subsets on the expression of CD14 and CD163. Furthermore, like human and mouse, pig monocytes also exhibited variation in CD16 expression, having a subset which was CD14hiCD16lo and another which was CD14loCD16hi. A whole genome approach was then used to study the differences between the monocyte subsets in the pig, using monocytes sorted into two populations based on the expression of CD14 and CD163. The gene expression profiles obtained were then compared to publically available data from monocyte subsets in human and mouse. This thesis also investigated the expression of genes that are known to be differentially expressed between human and mouse. To do this gene expression in porcine bone marrow derived macrophages was analyzed across an LPS time course. Like human macrophages, pig macrophages did not induce nitric oxide nor any arginine metabolizing genes in response to LPS. Instead they responded with robust induction of indoleamine 2,3-dioxygenase (IDO) and other enzymes of the tryptophan metabolism pathway such as kynurenine hydroxylase, kynureninase and tryptophan-tRNA synthetase. The tryptophan metabolism pathway has been implicated in sepsis in man and the absence of this pathway in the mouse may be one of the reasons why an adequate rodent model of sepsis has not been developed. The IDO inhibitor 1-methyl-tryptophan (1-MT) has been used to treat mouse macrophages where it had a protective effect after LPS administration. Similar experiments on pig macrophages did not show the same protective effect and induction of key immune genes was increased after treatment with 1-MT suggesting IDO is involved in feedback control of the immune system. With the completion of the genome sequence and the characterisation of many key regulators and markers, the pig has emerged as a tractable model of human innate immunity and disease that should address the limited predictive value of rodents in preclinical studies. This project aimed to address the gap in our knowledge of the control of innate immunity in the pig and provided further evidence that the pig can function as an ideal model to study innate immunity.
Transcriptional Regulation Of Prostaglandin H Synthase Pghs 2 Gene In A Macrophage Model Of Inflammation
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Author : Yeon-Joo Kang
language : en
Publisher:
Release Date : 2006
Transcriptional Regulation Of Prostaglandin H Synthase Pghs 2 Gene In A Macrophage Model Of Inflammation written by Yeon-Joo Kang and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2006 with Cyclooxygenases categories.
Transcriptional Regulation Of Macrophage Migration Inhibitory Factor
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Author : Lili Li
language : en
Publisher:
Release Date : 2006
Transcriptional Regulation Of Macrophage Migration Inhibitory Factor written by Lili Li and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2006 with categories.
