Interferon-λs: New Regulators of Inflammatory Processes
Title | Interferon-λs: New Regulators of Inflammatory Processes PDF eBook |
Author | Ivan Zanoni |
Publisher | Frontiers Media SA |
Pages | 120 |
Release | 2020-01-14 |
Genre | |
ISBN | 2889633055 |
Regulation of Interferon Regulatory Factors in LPS-Stimulated Macrophages
Title | Regulation of Interferon Regulatory Factors in LPS-Stimulated Macrophages PDF eBook |
Author | |
Publisher | |
Pages | 5 |
Release | 1995 |
Genre | |
ISBN |
Macrophages secrete interferons (IFNs), as well as other inflammatory cytokines, following stimulation with lipopolysaccharide (LPS), the outer membrane component of Gram negative bacteria that has been implicated as the initiator of the sepsis-associated Systemic Inflammatory Response Syndrome (SIRS). The interferon regulatory factors (IRFs) comprise a family of DNA binding proteins that positively and negtively regulate transcription of IFN and certain IFN-inducible genes. Basal and LPS-inducible levels of mRNA expressed by three IRF family member genes, i.e., IRF-1, IRF-2, and ICSBP, as well as a panel of other well characterized, SIRS-associated, inflammatory genes, were analyzed in macrophages derived from fully LPS-responsive mouse strains (Lps(n)), genetically LPS-hyporesponsive (Lps(d)) mice, IRF-1 and IRF-2 'knockout' mice, as well as from Lpsn macrophages rendered 'endotoxin tolerant' in vitro. Our results suggest that the IRF nuclear binding proteins, as well as serine/threonine phosphatases, play important roles in LPS-induced gene expression and may provide novel targets for therapeutic intervention, not only in Gram negative sepsis, but also in other syndromes characterized by inflammatory mediator excess.
Regulation of Inflammatory Signaling in Health and Disease
Title | Regulation of Inflammatory Signaling in Health and Disease PDF eBook |
Author | Dakang Xu |
Publisher | Springer |
Pages | 254 |
Release | 2017-09-18 |
Genre | Medical |
ISBN | 981105987X |
This book discusses recent research in innate immunity, which has revealed a large number of receptors that sense the presence of microorganisms or cellular damage in tissues. In complex tissues, many of these sensing events occur simultaneously. Thus, the downstream signaling pathways need to be integrated so that an appropriate cellular inflammatory response can be initiated. In addition, the inflammasome defines the molecular and cellular processes of inflammation in response to microbial infection. Previous data suggested that regulation of inflammasomes is mediated by microbes, but inflammasomes also have antimicrobial functions. Increasing evidence in mouse models, together with human data, strongly implicates an involvement of the inflammasome and uncontrolled inflammation in the initiation and progression of diseases with a high impact on public health. The book reviews novel aspects of functional genomics, epigenomics, transcriptomics, post-translat ional modifications, microbiome and immunometabolism in order to understand inflammatory signaling and responses, covering recent findings on the mechanisms underlying the regulation of inflammatory responses to pathogens, dysregulation of these responses in inflammatory disease, and the use of such mechanisms to boost or subdue the inflammatory response. Bridging the gaps in understanding between the fields of human and mouse immunology, it provides valuable insights into inflammatory-mediated disease and immune defense. Such innovative perspectives in both basic and clinical research promote the translation of knowledge to the clinic.
Fields Virology: Emerging Viruses
Title | Fields Virology: Emerging Viruses PDF eBook |
Author | Peter M. Howley |
Publisher | Lippincott Williams & Wilkins |
Pages | 2597 |
Release | 2020-02-11 |
Genre | Medical |
ISBN | 1975112555 |
Now in four convenient volumes, Field’s Virology remains the most authoritative reference in this fast-changing field, providing definitive coverage of virology, including virus biology as well as replication and medical aspects of specific virus families. This volume of Field’s Virology: Emerging Viruses, 7th Edition covers recent changes in emerging viruses, providing new or extensively revised chapters that reflect these advances in this dynamic field.
Characterizing Type I Interferon Mediated Inflammatory Response During Acute and Chronic Infections
Title | Characterizing Type I Interferon Mediated Inflammatory Response During Acute and Chronic Infections PDF eBook |
Author | Shankar Subramanian Iyer |
Publisher | |
Pages | 160 |
Release | 2013 |
Genre | |
ISBN |
During the course of infectious disease, the immune system generates a robust inflammatory response in order to eradicate the invading pathogen and restore tissue homeostasis. An essential feature of this process is the ability of the host to provide an anti-microbial response while preventing unnecessary collateral tissue damage. Many pro-inflammatory pathways, which contribute to host defense against infectious disease have been identified; however, the pathways that regulate and resolve the pro-inflammatory response preventing tissue injury are not well understood. To study the mechanisms by which the acute inflammatory response is resolved, we studied the Type I Interferon (IFN) pathway, a hallmark feature of acute phase immune response to viral infection, where induction of interferon stimulatory genes (ISGs) is required for host defense. In contrast, a strong type I IFN response often correlates with higher bacterial virulence and absence of a type I IFN response can enhance host-mediated clearance of many bacterial species. Therefore, it remains unknown whether the type I IFN response to bacterial infection is of benefit to the host and what the functional role might be. To elucidate the key regulatory pathways involved, we utilized RNA sequencing to identify a network of pro-inflammatory molecules that are transiently up-regulated but rapidly down-regulated in Toll like receptor (TLR) 4 stimulated mouse macrophages. Further studies in transgenic knockout animals revealed that the resolution of this pro-inflammatory network was dependent on type I IFN signaling as well as signaling of two type I IFN downstream targets, interleukin 27 (IL-27) and interleukin 10 IIL-10). Importantly in a model of acute systemic bacterial infection, abrogating the function of these molecules enhanced the host anti-microbial response, but concomitantly augmented inflammation including immune mediated organ damage resulting in increased mortality. Thus we have defined a type I IFN, IL-27 and IL-10 gene program, which is required for resolving acute inflammatory response to protect against tissue injury. Conversely we hypothesized that prolonged signaling by this pathway could create an immunosuppressive state conducive to the establishment or persistence of chronic infection. Utilizing a murine model of herpesgammavirus we demonstrate that defects in IL-27 or IL-10 signaling had little effect on active, lytic viral replication but prevented the establishment of viral latency. Thus we demonstrate how a single pathway can provide both beneficial and detrimental features in response to infectious disease.
Interferon Regulatory Factor 5 (IRF5)
Title | Interferon Regulatory Factor 5 (IRF5) PDF eBook |
Author | |
Publisher | |
Pages | |
Release | 2011 |
Genre | |
ISBN |
Molecular Biology of the Cell
Title | Molecular Biology of the Cell PDF eBook |
Author | |
Publisher | |
Pages | 0 |
Release | 2002 |
Genre | Cells |
ISBN | 9780815332183 |