Download or read book Production of Pro and Anti inflammatory Cytokines in Human Monocytes Regulation and Signaling written by and published by . This book was released on with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Cytokines and Pain written by L.R. Watkins and published by Springer. This book was released on 2013-03-08 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt: Within the past few years, it has become recognized that the immune system communicates to the brain. Substances released from activated immune cells (cytokines) stimulate peripheral nerves, thereby signaling the brain and spinal cord that infection/inflammation has occurred. Additionally, peripheral infection/inflammation leads to de novo synthesis and release of cytokines within the brain and spinal cord. Thus, cytokines effect neural activation both peripherally and centrally. Through this communication pathway, cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor markedly alter brain function, physiology and behavior. One important but underrecognized aspect of this communication is the dramatic impact that immune activation has on pain modulation. The purpose of this book is to examine, for the first time, immune-to-brain communication from the viewpoint of its effect on pain processing. It is aimed both at the basic scientist and health care providers, in order to clarify the major role that substances released by immune cells play in pain modulation. This book contains chapters contributed by all of the major laboratories focused on understanding how cytokines modulate pain. These chapters provide a unique vantage point from which to examine this question, as the summarized work ranges from evolutionary approaches across diverse species, to the basics of the immune response, to the effect of cytokines on peripheral and central nervous system sites, to therapeutic potential in humans.
Download or read book Regulatory Role of Monocytes and Macrophages in Infection and Immunity written by Adam Peres and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "The immune system uses a network of defense mechanisms that protects the host from infections. Although essential for host survival, this system can also be detrimental due to excessive inflammation and tissue damage. Therefore, hosts have evolved anti-inflammatory mechanisms aimed at controlling pro-inflammatory responses and contributing to host-commensal or -pathogen interactions and disease tolerance. Monocytes and macrophages are cells that are often the initiators and targets of both pro- and anti-inflammatory responses, and play major roles in the pathogenesis and regulation of many diseases. This thesis explored the role of two such immune-regulatory molecules, interleukin 10 (IL-10) and the aryl hydrocarbon receptor (AHR) in the regulation of monocyte responses.The first manuscript investigated the capacity of nasal Staphylococcus aureus isolates to induce the production of the anti-inflammatory cytokine IL-10 by human primary monocytes. Using laboratory strains of S. aureus, our lab had previously reported the importance of IL-10 in regulating T cell activation by staphylococcal superantigens (SAg). Here, we demonstrated that the induction of IL-10 by 16 nasal isolates of S. aureus differed by up to 3-fold. Mechanistically, the magnitude of IL-10 induction was due to differential degree of activation of the PI3K-Akt-mTOR pathway by S. aureus. The IL-10 response to S. aureus could also be uncoupled from the pro-inflammatory TNF-[alpha] response by both the signaling pathways used and the requirement for internalization and phagosome maturation. Lastly, the IL-10-inducing capacity of a nasal S. aureus isolate correlated with the suppression of SAg-induced T cell activation and lower Th1 cytokine production.The other manuscripts included in this thesis focused on the regulation of AHR in the context of monocyte and macrophage responses. We first examined the expression of the AHR gene program in monocytes during inflammation. To do this, we concomitantly stimulated human monocytes with either the toll-like receptor 4 (TLR4) ligand LPS or S. aureus, and an AHR ligand FICZ and found that LPS or S. aureus specifically blocked the induction of Cyp1a1 and Cyp1b1 mRNA. These enzymes metabolize AHR ligands to negatively regulate its activation. Interestingly, FICZ-induced CYP1 protein activity was restricted to monocyte-derived macrophages differentiated by GM-CSF (GM-MDMs) and was also regulated by LPS. Lastly, AHR ligands regulated cytokine production in GM-MDMs.Next, we explored the CYP1-AHR axis in the host response to endotoxin and endotoxin tolerance. Mice lacking AHR were more susceptible to endotoxemia than wild-type mice due to excessive cytokine production, but did not present an impairment in the establishment of endotoxin tolerance. We corroborated these findings in vitro using primary human monocytes. We also observed that, during endotoxemia, liver Cyp1a2 expression and activity was significantly reduced. We therefore hypothesized that Cyp1a2-deficient mice would be protected from LPS-driven immunopathology because of an increased bioavailability of AHR ligands that would dampen the inflammatory response by macrophages. However, we observed higher susceptibility of these mice to a primary LPS challenge. The mechanistic explanation for this finding is unclear and is still currently being investigated.Collectively, the work in this thesis furthered our understanding of the involvement of IL-10 and the AHR gene program in the immune regulatory role that monocytes and monocyte-derived macrophages play during commensalism and infectious diseases." --
Download or read book Pharmacology of Cytokines written by Alberto Mantovani and published by Oxford University Press, USA. This book was released on 2000 with total page 354 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cytokines are the "words" of immunity, serving as mediators within and outside the immune system. There is tremendous interest in their expliotation as therapeutic tools in diverse human diseases and considerable effort has been made to understand and utilize their pharmacology. This book examines this pharmacology, from developments and characterization of simple chemicals and their mechanism of action to the use of biotechnology-based approaches. The book puts cytokines and their pharmacology in context and examines their involvement in individual organ-disease systems.
Download or read book Inflammation and Cancer written by Bharat B. Aggarwal and published by Springer. This book was released on 2014-05-12 with total page 489 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.
Download or read book Regulation of Inflammation Its Resolution and Therapeutic Targeting written by Mariagrazia Uguccioni and published by Frontiers Media SA. This book was released on 2018-01-11 with total page 107 pages. Available in PDF, EPUB and Kindle. Book excerpt: Inflammation is a fundamental protective mechanism and at the same time the driving force of a variety of major diseases in humans. Indeed, acute self-resolving inflammation usually plays a positive role for the host, as exemplified by infectious diseases where its positive role is well established and testified by its perception as innate immunity. On the other hand, non-resolving inflammation and consequent chronicization is a key determinant of immunopathology and clinical manifestations of most major diseases in humans. As a consequence, it is increasing appreciated that the problem with inflammation is not how often it starts, but how often it fails to resolve. Appropriate resolution of inflammatory responses, which also drives activation of tissue damage repair mechanisms and return of local tissues to homeostasis, is a necessary process for ongoing health. Interestingly, cells sustaining these processes are also key to the proinflammatory responses, and the underlying “pro-resolving” molecular pathways are triggered as part of the pro-inflammatory response. This clearly indicates resolution of inflammation as an active process requiring functional repolarization of inflammatory cells that calls our attention on the underlying molecular mechanisms. The increasing number of anti-inflammatory drugs best-sellers in the pharma market is a clear indication of the relevance of having inflammation under check; nonetheless, there is still a great need for better acting pharmacological tools for the control of inflammation. Indeed, the remarkable success of biological drugs targeting proinflammatory cytokines has indicates that tools able to block proinflammatory mediators have promising applications, but at the same time has made clear that there are intrinsic limitations to this approach which frequently vanish undermine the activity of single targeting drugs, including the well-known redundancy of inflammatory mediators. Under self-limiting conditions inflammation spontaneously resolves in an active process. Some cellular and molecular mechanisms involved in inflammation resolution have been uncovered in the recent past, and include generation of specific cytokines, apoptosis of inflammatory leukocytes, lipid mediators, macrophage repolarization and others are likely to be revealed in the next future, since loss-of-function mutations of an increasing number of genes results in the development of spontaneous inflammation in experimental animals. We argue that “pushing for“ inflammation resolution by exploiting active naturally-occurring pro-resolving processes may have significant advantages over the attempt to simply “push back” inflammation by passive blockade of proinflammatory mediators. At present the research in the field of inflammation aims at identifying and validates new molecules involved in the resolution of inflammation as a basis for the development of innovative therapeutic strategies in chronic inflammatory and autoimmune diseases. This involves the discovery of new natural or synthetic “pro-resolving” molecules from plant and animals and the investigation of endogenous inflammation “pro-resolving” mechanisms, including atypical chemokine receptors, decoy receptors, and microRNA. An extensive effort is focused on the regulation by “pro-resolving” agents on two molecular systems of key relevance in inflammation: the chemokine system, which regulates recruitment, permanence and egress of leukocyte in tissues; and the Toll Like Receptor (TLR)/IL-1R system, which is central for the activation of infiltrating leukocytes.
Download or read book Human Monocytes written by Marek Zembala and published by . This book was released on 1989 with total page 584 pages. Available in PDF, EPUB and Kindle. Book excerpt: Monocytes represent one of the major types of white blood cells in man which prevent infection by ingesting and killing invading pathogens and by releasing factors which stimulate and regulate lymphocytes. Monocytes "purify" the blood, removing immune complexes, mediating inflammatory responses, and initiating tissue repair. Human Monocytes represents an up-to-date, definitive account of this important cell. It covers the cells biochemical, immunological, and inflammatory functionsand its role in many diseases, including asthma, atherosclerosis, rheumatoid arthritis, and AIDS.
Download or read book Regulation of Cytokine Expression During the Inflammatory Process written by Julia Yung Lee and published by . This book was released on 2002 with total page 143 pages. Available in PDF, EPUB and Kindle. Book excerpt: Monocytes and macrophages respond to bacterial components as a part of the innate immune response to fight off pathogenic infections. Various biologically active cytokines are produced to mediate the inflammatory process and stimulate a cascade of inflammatory mediators. A microenvironment is maintained to activate cells, clear pathogens, and contain the area of infection. We examine specifically two pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). The inappropriate or excessive production of these cytokines results in tissue damage and has implications in chronic inflammation and autoimmune diseases. TNF-alpha potently stimulates the production of other cytokines and adhesion molecules. It recruits other inflammatory cells and upregulates the adaptive immune response. We explore how TNF-alpha production is regulated by two mechanisms. We find that chromatin structures in the promoter region of the TNF-alpha gene are altered with maturation. In vitro human monocytic cell lines representing different stages of maturation demonstrate increasing histone H3 acetylation with increasing maturation. Primary human monocytes and macrophages also show similar phenomena. Increasing acetylation of histone H3 is associated with increasing responsiveness to stimulation. Another aspect of TNF-alpha gene regulation is examined from the perspective of signaling pathways initiated by IFN-gamma and lipopolysaccharide (LPS). We investigate how IFN-gamma may be able to potentiate the LPS-inducible TNF-alpha production in monocytes and determine that this occurred at the level of transcription. We also assess the role of IFN-gamma in pathogenesis of the autoimmune disease, systemic lupus erythematosus. Specifically, a dinucleotide repeat polymorphism in the first intron of the human IFN-gamma gene is associated with specific disease manifestations. Understanding how cytokines in the inflammatory process are regulated has important clinical significance. Controlling the aberrant production of these cytokines may be used therapeutically to prevent chronic inflammation and autoimmune conditions.
Download or read book Principles of Cancer Biotherapy written by Robert K. Oldham and published by Springer Science & Business Media. This book was released on 2009-08-29 with total page 743 pages. Available in PDF, EPUB and Kindle. Book excerpt: At the time of the first edition of Principles of Cancer Biotherapy in 1987, this book represented the first comprehensive textbook on biological therapy. In 1991, when the second edition was published, there was still some doubt on the part of many oncologists and cancer researchers as to the therapeutic value of these new approaches. By 2003 and the fourth edition, it was generally agreed that biopharmaceuticals were producing major opportunities for new cancer therapies. Cancer biotherapy has now truly matured into the fourth modality of cancer treatment. This fifth revised edition describes the tremendous progress that has been made in recent years using biologicals in cancer treatment. This book summarizes an evolving science and a rapidly changing medical practice in biotherapy. In this new millennium, it is now possible to envision a much more diversified system of cancer research and treatment that will afford greater opportunities for a patient’s personalized cancer treatment. This was first envisioned in the 1987 initial edition of this textbook and is now a “new” and popular approach to cancer treatment. Some forms of cancer biotherapy use the strategy of tumor stabilization and control through continued biological therapy, akin to the use of insulin in the treatment of diabetes. This textbook illustrates new methods of thinking and new strategies for control of cancer. It is always difficult to move from past dogma to future opportunity, but this fifth edition of Principles of Cancer Biotherapy illustrates why it is so important to the patients for researchers and clinicians to explore and quickly apply these new opportunities in cancer biotherapy.
Download or read book Cooperation of Liver Cells in Health and Disease written by Z. Kmiec and published by Springer Science & Business Media. This book was released on 2013-06-29 with total page 154 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Handbook on Immunosenescence written by Tamas Fulop and published by Springer Science & Business Media. This book was released on 2009-02-27 with total page 1693 pages. Available in PDF, EPUB and Kindle. Book excerpt: This authoritative handbook covers all aspects of immunosenescence, with contributions from experts in the research and clinical areas. It examines methods and models for studying immunosenescence; genetics; mechanisms including receptors and signal transduction; clinical relevance in disease states including infections, autoimmunity, cancer, metabolic syndrome, neurodegenerative diseases, frailty and osteoporosis; and much more.
Download or read book Nijkamp and Parnham s Principles of Immunopharmacology written by Michael J. Parnham and published by Springer Nature. This book was released on 2019-12-10 with total page 888 pages. Available in PDF, EPUB and Kindle. Book excerpt: Principles of Immunopharmacology provides a unique source of essential knowledge on the immune response, its diagnosis and its modification by drugs and chemicals. The 4th edition of this internationally recognized textbook has been revised to include recent developments, but continues the established format, dealing with four related fields in a single volume, thus obviating the need to refer to several different textbooks. The first section of the book, providing a basic introduction to immunology and its relevance for human disease, has been updated to accommodate new immunological concepts, particularly the role of epigenetics and the latest understanding of cancer immunology. The second section on immunodiagnostics offers a topical description of widely used molecular techniques and a new chapter on imaging techniques. This is followed by a systematic coverage of drugs affecting the immune system, including natural products. This third section contains 15 updated chapters, covering classical immunopharmacological topics such as anti-asthmatic, anti-rheumatic and immunosuppressive drugs, but also deals with antibiotics, plant-derived and dietary agents, with new chapters on monoclonal antibodies, immunotherapy in sepsis and infection, drugs for soft-tissue autoimmunity and cell therapy. The book concludes with a chapter on immunotoxicology and drug safety tests. Aids to the reader include a two-column format, glossaries of technical terms and appendix reference tables. The emphasis on illustrations is maintained from the first three editions. The book is a valuable single reference for undergraduate and graduate medical and biomedical students, postgraduate chemistry and pharmacy students, researchers in chemistry, biochemistry and the pharmaceutical industry and researchers lacking basic immunological knowledge, who want to understand the actions of drugs on the immune system.
Download or read book SHP 1 Src Complex is a Master Regulator of the IL 12 IL 23 Pro and IL 10 IL 27 Anti inflammatory Axis in TLR4 activated Signaling Pathways in Human Monocytes and Macrophages written by Yulia Konarski and published by . This book was released on 2013 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Although the etiology surrounding many autoimmune diseases remains unknown, the underlying characteristic of many of these diseases is a disruption in the balance of pro- and anti- inflammatory cytokines It is well established that the dysregulation of the IL-12 family of cytokines, an increase in IL-12/IL-23 and a decrease in IL-27 production has been implicated in these conditions. We used ELISA, RT-PCR, Immunofluorescence and Western immunoblotting in conjunction with pharmalogical inhibitors and siRNA to demonstrate the role of SHP-1/Src in the regulation of IL-12, IL-23, IL-27 and IL-10 in LPS-stimulated human THP-1 cells, monocytes and MDMs. My results show for the first time that Src kinase activity relies on SHP-1 activity, and together this complex functions in TLR4-mediated MyD88 and TRIF pathways. Furthermore Src exhibits a dual role as a positive regulator for anti-inflammatory IL-10/IL-27 and as a negative regulator of pro-inflammatory IL-12/IL-23 downstream of TLR4. Moreover, the involvement of PI3K and JNK MAPK, dependent on SHP-1/Src complex, in the regulation of IL-12 family and IL-10 downstream of TLR4 was shown.
Download or read book IL 1 beta and SIL 1Ra Production in Acute and Chronic Inflammation written by Karim Brandt and published by . This book was released on 2010 with total page 338 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Neuroscience in the 21st Century written by Donald W. Pfaff and published by Springer. This book was released on 2016-10-27 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Edited and authored by a wealth of international experts in neuroscience and related disciplines, this key new resource aims to offer medical students and graduate researchers around the world a comprehensive introduction and overview of modern neuroscience. Neuroscience research is certain to prove a vital element in combating mental illness in its various incarnations, a strategic battleground in the future of medicine, as the prevalence of mental disorders is becoming better understood each year. Hundreds of millions of people worldwide are affected by mental, behavioral, neurological and substance use disorders. The World Health Organization estimated in 2002 that 154 million people globally suffer from depression and 25 million people from schizophrenia; 91 million people are affected by alcohol use disorders and 15 million by drug use disorders. A more recent WHO report shows that 50 million people suffer from epilepsy and 24 million from Alzheimer’s and other dementias. Because neuroscience takes the etiology of disease—the complex interplay between biological, psychological, and sociocultural factors—as its object of inquiry, it is increasingly valuable in understanding an array of medical conditions. A recent report by the United States’ Surgeon General cites several such diseases: schizophrenia, bipolar disorder, early-onset depression, autism, attention deficit/ hyperactivity disorder, anorexia nervosa, and panic disorder, among many others. Not only is this volume a boon to those wishing to understand the future of neuroscience, it also aims to encourage the initiation of neuroscience programs in developing countries, featuring as it does an appendix full of advice on how to develop such programs. With broad coverage of both basic science and clinical issues, comprising around 150 chapters from a diversity of international authors and including complementary video components, Neuroscience in the 21st Century in its second edition serves as a comprehensive resource to students and researchers alike.
Download or read book Cytokines and the CNS written by Richard M. Ransohoff and published by CRC Press. This book was released on 2005-10-31 with total page 379 pages. Available in PDF, EPUB and Kindle. Book excerpt: Provides Insight into How Cytokine Action Impacts the Physiology and Pathology of the CNS. As with the first edition of Cytokines and the CNS, this completely updated and revised edition introduces neurobiologists to cytokine biology and immunologists to the unique functions of cytokines in CNS physiology. The dramatically accelera
Download or read book Anti inflammatory Cytokine Production written by Meha Bhargava and published by . This book was released on 2011 with total page 39 pages. Available in PDF, EPUB and Kindle. Book excerpt: The interleukin 1 receptor (IL-1R) and the Toll-like receptors (TLRs) are highly homologous innate immune receptors that provide the first line of defense against infection. We show that IL-1R type I (IL-1RI) is essential for TLR9-dependent activation of tumor necrosis factor receptor-associated factor 3 (TRAF3) and for production of the anti-inflammatory cytokines IL-10 and type I interferon (IFN). Noncanonical K63-linked ubiquitination of TRAF3, which is essential for type I IFN and IL-10 production, was impaired in Il1r1-/- CD11 c+ dendritic cells. In contrast, degradative ubiquitination of TRAF3 was not affected in the absence of IL-1R1 signaling. Deubiquitinating enzyme A (DUBA), which selectively cleaves K63-linked ubiquitin chains from TRAF3, was up-regulated in the absence of IL-1R1 signaling. DUBA short interference RNA augmented the TLR9-dependent type I IFN response. Mice deficient in IL-1RI signaling showed reduced expression of IL-10 and type I IFN and increased susceptibility to dextran sulphate sodium-induced colitis and failed to mount a protective type I IFN response after TLR9 ligand (CpG) administration. Our data identifies a new molecular pathway by which IL-1 signaling attenuates TLR9-mediated proinflammatory responses.
