Role Of Proteolytic Processing Of Tumor Necrosis Factor Alpha In Immunopathology During Influenza Infection
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Author | : Matthew Peter DeBerge |
Publisher | : |
Total Pages | : 464 |
Release | : 2013 |
Genre | : |
ISBN | : |
Influenza virus is a respiratory pathogen that is capable of causing considerable pulmonary pathology and respiratory dysfunction in humans. Seasonal influenza epidemics and the occasional influenza pandemic are responsible for significant morbidity and mortality and represent challenging economic and public health burdens. It is largely believed that a dysregulated host immune response can contribute to the severity of disease seen in humans infected with influenza virus. The goal of the studies outlined in the dissertation was to identify elements of the host response that exacerbate lung injury during influenza infection. We hypothesized that proteolytic processing of tumor necrosis factor (TNF)-[alpha] was a critical event regulating immunopathology during influenza infection. The first aim was to examine the role of TNF-[alpha] processing in viral clearance and the host response to influenza viral challenge in mice. The second aim was to investigate the specific contribution of TNF-[alpha] processing by influenza-specific CD8 T cells for the development of acute lung injury in a transgenic mouse model of influenza infection. The third aim was designed to determine the mechanisms by which CD8+ T cells regulated TNF-[alpha] processing. Whereas, TNF-[alpha] processing was required in the whole animal during a sub-lethal influenza infection to limit the immune response and the extent of lung injury, we found that specific inhibition of TNF-[alpha] processing by influenza-specific CD8+ T cells mitigated severe and lethal lung injury in a transgenic mouse model of highly pathogenic influenza infection. Moreover, we show that T-cell receptor signaling can induce proteolytic processing and this process is dependent on the MAPK/ERK signaling pathway. These studies highlight the complex nature of TNF-[alpha] processing and demonstrate that the outcome of this event is influenced in part by the viral load and cellular source of TNF-[alpha]. To our knowledge, these studies are the first to show that proteolytic processing of TNF-[alpha] is a critical event regulating the host immune response and severity of disease during influenza infection in mice. The protection or pathology observed in these studies following inhibition of TNF-[alpha] processing may have important implications for attenuating immunopathology during influenza infection in humans.
Author | : Ah-Ng Tony Kong |
Publisher | : CRC Press |
Total Pages | : 631 |
Release | : 2016-04-19 |
Genre | : Medical |
ISBN | : 1466503718 |
Increasing scientific evidence suggests that the majority of diseases including cancer are driven by oxidative stress and inflammation, attributed to environmental factors. These factors either drive genetic mutations or epigenetically modify expression of key regulatory genes. These changes can occur as early as gestational fetal development, and
Author | : Bharat B. Aggarwal |
Publisher | : Springer |
Total Pages | : 489 |
Release | : 2014-05-12 |
Genre | : Medical |
ISBN | : 3034808372 |
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.
Author | : Sajal Chakraborti |
Publisher | : Springer |
Total Pages | : 516 |
Release | : 2017-07-13 |
Genre | : Medical |
ISBN | : 9811031622 |
This book bridges the gap between fundamental research and biomedical and pharmacological applications on proteases. It represents a comprehensive overview of the multifaceted field of proteases in cellular environment and highlights the recently elucidated functions of complex proteolytic systems in different diseases. Several established investigators have elucidated the crucial role of proteases in biological processes, including how proteolytic function and regulation can be combined to develop new strategies of therapeutic interventions. Proteases form one of the largest and most diverse families of enzymes known. It is now clear that proteases are involved in every aspect of life functions of an organism. Under physiological conditions, proteases are regulated by their endogenous inhibitors; however, when the activity of proteases is not regulated appropriately, disease processes can result in. So, there is absolute need for a stringent control of proteolytic activities in cells and tissues. Dysregulation of proteases may cause derangement of cellular signalling network resulting in different pathophysiological conditions such as vascular remodelling, atherosclerotic plaque progression, ulcer and rheumatoid arthritis, Alzheimer disease, cancer metastasis, tumor progression and inflammation. Additionally, many infective microorganisms require proteases for replication or use proteases as virulence factors, which have facilitated the development of protease-targeted therapies for a variety of parasitic diseases.
Author | : Steven A. Frank |
Publisher | : Princeton University Press |
Total Pages | : 364 |
Release | : 2002-07-21 |
Genre | : Medical |
ISBN | : 9780691095950 |
Author | : Christopher J. Burrell |
Publisher | : Academic Press |
Total Pages | : 604 |
Release | : 2016-11-09 |
Genre | : Science |
ISBN | : 0123751578 |
Fenner and White's Medical Virology, Fifth Edition provides an integrated view of related sciences, from cell biology, to medical epidemiology and human social behavior. The perspective represented by this book, that of medical virology as an infectious disease science, is meant to provide a starting point, an anchor, for those who must relate the subject to clinical practice, public health practice, scholarly research, and other endeavors. The book presents detailed exposition on the properties of viruses, how viruses replicate, and how viruses cause disease. These chapters are then followed by an overview of the principles of diagnosis, epidemiology, and how virus infections can be controlled. The first section concludes with a discussion on emergence and attempts to predict the next major public health challenges. These form a guide for delving into the specific diseases of interest to the reader as described in Part II. This lucid and concise, yet comprehensive, text is admirably suited to the needs of not only advanced students of science and medicine, but also postgraduate students, teachers, and research workers in all areas of virology. Features updated and expanded coverage of pathogenesis and immunity Contains the latest laboratory diagnostic methods Provides insights into clinical features of human viral disease, vaccines, chemotherapy, epidemiology, and control
Author | : Balz Frei |
Publisher | : Academic Press |
Total Pages | : 624 |
Release | : 1994-09-22 |
Genre | : Health & Fitness |
ISBN | : |
This book serves as a comprehensive overview of the current scientific knowledge on the health effects of dietary and supplemental antioxidants (such as vitamins C and E). Chapters integrate information from basic research and animal studies, epidemiologic studies, and clinical intervention trials. The popular media has taken great interest in antioxidants, with numerous articles emphasizing their role in preventing disease and the possible slowing of the aging process. These antioxidant vitamins may be important in preventing not only acute deficiency symptoms, but also chronic disorders such as heart disease and certain types of cancer. This book, therefore, is not only for scientists and doctors, but also for health writers, journalists, and informed lay people. The text focuses on several human conditions for which there is now good scientific evidence that oxidation is an important etiological component. Specifically, antioxidants may prevent or slow down the progression of: Cancer, Cardiovascular disease, Immune system disorders, Cataracts, Neurological disorders, Degeneration due to the aging process.
Author | : Jean-Louis Vincent |
Publisher | : Springer |
Total Pages | : 520 |
Release | : 2017-03-31 |
Genre | : Medical |
ISBN | : 3319519085 |
The Annual Update compiles reviews of the most recent developments in experimental and clinical intensive care and emergency medicine research and practice in one comprehensive reference book. The chapters are written by well recognized experts in these fields. The book is addressed to everyone involved in internal medicine, anesthesia, surgery, pediatrics, intensive care and emergency medicine.
Author | : Gennaro Ciliberto |
Publisher | : CRC Press |
Total Pages | : 392 |
Release | : 2000-11-14 |
Genre | : Medical |
ISBN | : 9780203904244 |
Compiling an up-to-date and detailed survey of the role cytokines play in cell-to-cell communication, development, and differentiation, this comprehensive reference highlights the medical advantages of cytokine inhibition and pursues novel methods of discovery for more potent and specific blocking agents. Investigates the pathogenic role of
Author | : Adriano Rossi |
Publisher | : Springer Science & Business Media |
Total Pages | : 246 |
Release | : 2008-03-17 |
Genre | : Medical |
ISBN | : 376437506X |
This book provides readers with an up-to-date and comprehensive view on the resolution of inflammation and on new developments in this area, including pro-resolution mediators, apoptosis, macrophage clearance of apoptotic cells, possible novel drug developments.