The Experts below are selected from a list of 418293 Experts worldwide ranked by ideXlab platform
Peter A Ward - One of the best experts on this subject based on the ideXlab platform.
-
Leukocyte Recruitment and the Acute Inflammatory Response
Brain pathology (Zurich Switzerland), 2006Co-Authors: Paul Kubes, Peter A WardAbstract:Leukocyte recruitment is a hallmark feature of the Inflammatory Response. This review summarizes the generally accepted paradigm of leukocyte recruitment based on studies using intravital microscopy to visualize the microcirculation. The role of selectins and alpha4-integrin in rolling as well as integrin-mediated adhesion is discussed. However, it is becoming increasingly clear that the recruitment cascade within organs differs and therefore the review also attempts to highlight what is and is not known regarding leukocyte recruitment into the brain microvasculature. In the second part of this review, we provide some discussion of mechanisms by which the Inflammatory Response may be terminated. Particular emphasis on nuclear factor Nf kappaB and how IL10, IL13 and secreted leukocyte protease inhibitor (SLPI) may impact upon the Nf kappaB-dependent Inflammatory Response is presented.
-
Mechanisms of Inflammatory Response syndrome in sepsis
Drug Discovery Today: Disease Mechanisms, 2004Co-Authors: Laszlo M. Hoesel, Peter A WardAbstract:The systemic Inflammatory Response syndrome (SIRS) and sepsis are accompanied by a complex, unbalanced and often fatal activation of the immune and Inflammatory systems. Although the mechanisms are not yet completely explored, a variety of infectious and non-infectious conditions can lead to hyperactive Inflammatory Responses at the onset of sepsis, followed by immunoparalysis, compromised immune function and defective innate immune Responses at a later stage.
-
Endogenous regulation of the acute Inflammatory Response.
Molecular and cellular biochemistry, 2002Co-Authors: Peter A Ward, Alex B LentschAbstract:The acute Inflammatory Response has been triggered in rat lungs by deposition of IgG immune complexes. The Inflammatory reaction triggered is highly tissue damaging and requires activation of NF-kappaB with ensuing generation of chemokines and cytokines. Endogenous generation of IL- 10 and IL- 13 as well as secretory leukocyte protease inhibitor (SLPI), significantly regulates this Inflammatory Response. IL-10 and IL-13 attenuate NF-kappaB activation by interfering with breakdown of IkappaBalpha, while SLPI likewise suppresses NF-kappaB activation, but by interfering with breakdown of IkappaBbeta. Antibody induced blockade of IL-10, IL-13 or SLPI enhances NF-KB activation in lung and exacerbates the lung Inflammatory Response and injury. These data indicate that endogenous IL-10, IL-13 and SLPI are important regulators of the Inflammatory Response by reducing gene activation with resultant generation of peptide mediators/cytokines and chemokines.
-
Endogenous regulation of the acute Inflammatory Response.
Oxygen Nitrogen Radicals: Cell Injury and Disease, 2002Co-Authors: Peter A Ward, Alex B LentschAbstract:The acute Inflammatory Response has been triggered in rat lungs by deposition of IgG immune complexes. The Inflammatory reaction triggered is highly tissue damaging and requires activation of NF-кB with ensuing generation of chemokines and cytokines. Endogenous generation of IL-10 and IL-13 as well as secretory leukocyte protease inhibitor (SLPI), significantly regulates this Inflammatory Response. IL-10 and IL-13 attenuate NF-кB activation by interfering with breakdown of IKBa, while SLPI likewise suppresses NF-кB activation, but by interfering with breakdown of IKBs. Antibody induced blockade of IL-10, IL-13 or SLPI enhances NF-кB activation in lung and exacerbates the lung Inflammatory Response and injury. These data indicate that endogenous IL-10, IL-13 and SLPI are important regulators of the Inflammatory Response by reducing gene activation with resultant generation of peptide mediators/cytokines and chemokines. (Mol Cell Biochem 234/235: 225–228, 2002)
-
The acute Inflammatory Response and its regulation
Archives of surgery (Chicago Ill. : 1960), 1999Co-Authors: Peter A Ward, Alex B LentschAbstract:The acute Inflammatory Response is composed of an elaborate cascade of both proInflammatory and anti-Inflammatory mediators. The balance between these mediators often determines the outcome after injury. In clinical scenarios, such as trauma or sepsis, there is often unregulated production of proInflammatory mediators that can cause multiple organ failure. Further understanding of the endogenous mechanisms that control the Inflammatory Response is needed to facilitate development of therapeutic options. In this review, we discuss the current knowledge of the mechanisms leading to development of acute Inflammatory injury as well as the factors that regulate this Response.
Alex B Lentsch - One of the best experts on this subject based on the ideXlab platform.
-
Endogenous regulation of the acute Inflammatory Response.
Molecular and cellular biochemistry, 2002Co-Authors: Peter A Ward, Alex B LentschAbstract:The acute Inflammatory Response has been triggered in rat lungs by deposition of IgG immune complexes. The Inflammatory reaction triggered is highly tissue damaging and requires activation of NF-kappaB with ensuing generation of chemokines and cytokines. Endogenous generation of IL- 10 and IL- 13 as well as secretory leukocyte protease inhibitor (SLPI), significantly regulates this Inflammatory Response. IL-10 and IL-13 attenuate NF-kappaB activation by interfering with breakdown of IkappaBalpha, while SLPI likewise suppresses NF-kappaB activation, but by interfering with breakdown of IkappaBbeta. Antibody induced blockade of IL-10, IL-13 or SLPI enhances NF-KB activation in lung and exacerbates the lung Inflammatory Response and injury. These data indicate that endogenous IL-10, IL-13 and SLPI are important regulators of the Inflammatory Response by reducing gene activation with resultant generation of peptide mediators/cytokines and chemokines.
-
Endogenous regulation of the acute Inflammatory Response.
Oxygen Nitrogen Radicals: Cell Injury and Disease, 2002Co-Authors: Peter A Ward, Alex B LentschAbstract:The acute Inflammatory Response has been triggered in rat lungs by deposition of IgG immune complexes. The Inflammatory reaction triggered is highly tissue damaging and requires activation of NF-кB with ensuing generation of chemokines and cytokines. Endogenous generation of IL-10 and IL-13 as well as secretory leukocyte protease inhibitor (SLPI), significantly regulates this Inflammatory Response. IL-10 and IL-13 attenuate NF-кB activation by interfering with breakdown of IKBa, while SLPI likewise suppresses NF-кB activation, but by interfering with breakdown of IKBs. Antibody induced blockade of IL-10, IL-13 or SLPI enhances NF-кB activation in lung and exacerbates the lung Inflammatory Response and injury. These data indicate that endogenous IL-10, IL-13 and SLPI are important regulators of the Inflammatory Response by reducing gene activation with resultant generation of peptide mediators/cytokines and chemokines. (Mol Cell Biochem 234/235: 225–228, 2002)
-
The acute Inflammatory Response and its regulation
Archives of surgery (Chicago Ill. : 1960), 1999Co-Authors: Peter A Ward, Alex B LentschAbstract:The acute Inflammatory Response is composed of an elaborate cascade of both proInflammatory and anti-Inflammatory mediators. The balance between these mediators often determines the outcome after injury. In clinical scenarios, such as trauma or sepsis, there is often unregulated production of proInflammatory mediators that can cause multiple organ failure. Further understanding of the endogenous mechanisms that control the Inflammatory Response is needed to facilitate development of therapeutic options. In this review, we discuss the current knowledge of the mechanisms leading to development of acute Inflammatory injury as well as the factors that regulate this Response.
-
Regulation of the Lung Inflammatory Response
Sepsis and Organ Dysfunction, 1999Co-Authors: Peter A Ward, Alex B LentschAbstract:Lung Inflammatory Responses in rat lung induced by deposition of IgG immune complexes are associated with complement activation, influx of neutrophils, activation of pulmonary macrophages and ensuing injury of the lung parenchyma [1]. Injury in this model is associated with extravascular leak of albumin, development of haemorrhage and damage of cellular and matrix constituents. Tissue injury is likely due to the combined effects of oxidants and proteases released from activated lung macrophages and from recruited neutrophils following a complex sequence of cellular and mediator interactions [2]. Essential to an understanding of these Inflammatory events is the relationship between lung macrophage production of cytokines [such as tumor necrosis factor-alpha (TNFα) and interleukin-1 (IL-1)] and the Response of the lung vasculature, the result of which is upregulation of endothelial adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and E-selectin. We have found that these lung Inflammatory reactions are carefully self-regulated. That is to say, the intensity of the Inflammatory Response builds up to a crescendo, peaking between 3–4 hours, then rapidly diminishes, as reflected by a reduction in vascular permeability, a cessation in haemorrhage and no further accumulation of neutrophils [3]. In some manner, then, these Inflammatory Responses are under regulatory control that ensures the potentially destructive Inflammatory Response will be contained.
Gertrud Maria Hänsch - One of the best experts on this subject based on the ideXlab platform.
-
On the Inflammatory Response in metal-on-metal implants.
Journal of translational medicine, 2014Co-Authors: Ulrike Dapunt, Thomas Giese, Felix Lasitschka, Jörn Reinders, Burkhard Lehner, Jan Philippe Kretzer, Volker Ewerbeck, Gertrud Maria HänschAbstract:Background Metal-on-metal implants are a special form of hip endoprostheses that despite many advantages can entail serious complications due to release of wear particles from the implanted material. Metal wear particles presumably activate local host defence mechanisms, which causes a persistent Inflammatory Response with destruction of bone followed by a loosening of the implant. To better characterize this Inflammatory Response and to link inflammation to bone degradation, the local generation of proInflammatory and osteoclast-inducing cytokines was analysed, as was systemic T cell activation.
Craig M. Coopersmith - One of the best experts on this subject based on the ideXlab platform.
-
The systemic Inflammatory Response syndrome.
Microbes and infection, 2006Co-Authors: Charles M. Robertson, Craig M. CoopersmithAbstract:The systemic Inflammatory Response syndrome (SIRS) is the body's Response to an infectious or noninfectious insult. Although the definition of SIRS refers to it as an "Inflammatory" Response, it actually has pro- and anti-Inflammatory components. This review outlines the pathophysiology of SIRS and highlights potential targets for future therapeutic intervention in patients with this complex entity.
Nikolaos G Frangogiannis - One of the best experts on this subject based on the ideXlab platform.
-
the Inflammatory Response in myocardial injury repair and remodelling
Nature Reviews Cardiology, 2014Co-Authors: Nikolaos G FrangogiannisAbstract:Myocardial infarction triggers an intense Inflammatory Response that is essential for cardiac repair, but which is also implicated in the pathogenesis of postinfarction remodelling and heart failure. Signals in the infarcted myocardium activate toll-like receptor signalling, while complement activation and generation of reactive oxygen species induce cytokine and chemokine upregulation. Leukocytes recruited to the infarcted area, remove dead cells and matrix debris by phagocytosis, while preparing the area for scar formation. Timely repression of the Inflammatory Response is critical for effective healing, and is followed by activation of myofibroblasts that secrete matrix proteins in the infarcted area. Members of the transforming growth factor β family are critically involved in suppression of inflammation and activation of a profibrotic programme. Translation of these concepts to the clinic requires an understanding of the pathophysiological complexity and heterogeneity of postinfarction remodelling in patients with myocardial infarction. Individuals with an overactive and prolonged postinfarction Inflammatory Response might exhibit left ventricular dilatation and systolic dysfunction and might benefit from targeted anti-IL-1 or anti-chemokine therapies, whereas patients with an exaggerated fibrogenic reaction can develop heart failure with preserved ejection fraction and might require inhibition of the Smad3 (mothers against decapentaplegic homolog 3) cascade. Biomarker-based approaches are needed to identify patients with distinct pathophysiologic Responses and to rationally implement inflammation-modulating strategies.
-
the Inflammatory Response in myocardial infarction
Cardiovascular Research, 2002Co-Authors: Nikolaos G Frangogiannis, Wayne C Smith, Mark L EntmanAbstract:One of the major therapeutic goals of modern cardiology is to design strategies aimed at minimizing myocardial necrosis and optimizing cardiac repair following myocardial infarction. However, a sound understanding of the biology is necessary before a specific intervention is pursued on a therapeutic basis. This review summarizes our current understanding of the cellular and molecular mechanisms regulating the Inflammatory Response following myocardial ischemia and reperfusion. Myocardial necrosis induces complement activation and free radical generation, triggering a cytokine cascade initiated by Tumor Necrosis Factor (TNF)-α release. If reperfusion of the infarcted area is initiated, it is attended by an intense Inflammatory reaction. Interleukin (IL)-8 synthesis and C5a activation have a crucial role in recruiting neutrophils in the ischemic and reperfused myocardium. Neutrophil infiltration is regulated through a complex sequence of molecular steps involving the selectins and the integrins, which mediate leukocyte rolling and adhesion to the endothelium. Marginated neutrophils exert potent cytotoxic effects through the release of proteolytic enzymes and the adhesion with Intercellular Adhesion Molecule (ICAM)-1 expressing cardiomyocytes. Despite this potential injury, substantial evidence suggests that reperfusion enhances cardiac repair improving patient survival; this effect may be in part related to the Inflammatory Response. Monocyte Chemoattractant Protein (MCP)-1 is also markedly upregulated in the infarcted myocardium inducing recruitment of mononuclear cells in the injured areas. Monocyte-derived macrophages and mast cells may produce cytokines and growth factors necessary for fibroblast proliferation and neovascularization, leading to effective repair and scar formation. At this stage expression of inhibitory cytokines such as IL-10 may have a role in suppressing the acute Inflammatory Response and in regulating extracellular matrix metabolism. Fibroblasts in the healing scar undergo phenotypic changes expressing smooth muscle cell markers. Our previous review in this journal focused almost exclusively on reduction of the Inflammatory injury. The current update is prompted by the potential therapeutic opportunity that the open vessel offers. By promoting more effective tissue repair, it may be possible to reduce the deleterious remodeling, that is the leading cause of heart failure and death. Elucidating the complex interactions and regulatory mechanisms responsible for cardiac repair may allow us to design effective inflammation-related interventions for the treatment of myocardial infarction.
