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Articles 1 - 6 of 6
Full-Text Articles in Hepatology
Inflammasomes In Liver Diseases, Gyongyi Szabo, Timea Csak
Inflammasomes In Liver Diseases, Gyongyi Szabo, Timea Csak
Gyongyi Szabo
Inflammation is a common element in the pathogenesis of most chronic liver diseases that lead to fibrosis and cirrhosis. Inflammation is characterized by activation of innate immune cells and production of pro-inflammatory cytokines IL-1alpha, IL-1beta, and TNFalpha. Inflammasomes are intracellular multiprotein complexes expressed in both parenchymal and non-parenchymal cells of the liver that in response to cellular danger signals activate caspase-1, and release IL-1beta and IL-18. The importance of inflammasome activation in various forms of liver diseases in relation to liver damage, steatosis, inflammation and fibrosis is discussed in this review. Elsevier B.V. All rights reserved.
Hypoxia And Hypoxia Inducible Factors: Diverse Roles In Liver Diseases, Bharath Nath, Gyongyi Szabo
Hypoxia And Hypoxia Inducible Factors: Diverse Roles In Liver Diseases, Bharath Nath, Gyongyi Szabo
Gyongyi Szabo
Hypoxia has been shown to have a role in the pathogenesis of several forms of liver disease. The hypoxia inducible factors (HIFs) are a family of evolutionarily conserved transcriptional regulators that affect a homeostatic response to low oxygen tension and have been identified as key mediators of angiogenesis, inflammation, and metabolism. In this review we summarize the evidence for a role of HIFs across a range of hepatic pathophysiology. We describe regulation of the HIFs and review investigations that demonstrate a role for HIFs in the development of liver fibrosis, activation of innate immune pathways, hepatocellular carcinoma, as well as …
An Essential Role For Monocyte Chemoattractant Protein-1 In Alcoholic Liver Injury: Regulation Of Proinflammatory Cytokines And Hepatic Steatosis In Mice, Pranoti Mandrekar, Aditya Ambade, Arlene Lim, Gyongyi Szabo, Donna Catalano
An Essential Role For Monocyte Chemoattractant Protein-1 In Alcoholic Liver Injury: Regulation Of Proinflammatory Cytokines And Hepatic Steatosis In Mice, Pranoti Mandrekar, Aditya Ambade, Arlene Lim, Gyongyi Szabo, Donna Catalano
Gyongyi Szabo
The importance of chemokines in alcoholic liver injury has been implicated. The role of the chemokine, monocyte chemoattractant protein-1 (MCP-1), elevated in patients with alcoholic liver disease is not yet understood. Here, we evaluated the pathophysiological significance of MCP-1 and its receptor, chemokine (C-C motif) receptor 2 (CCR2), in alcoholic liver injury. The Leiber-DeCarli diet containing alcohol or isocaloric control diets were fed to wild-type (WT) and MCP-1-deficient knockout (KO) mice for 6 weeks. In vivo and in vitro assays were performed to study the role of MCP-1 in alcoholic liver injury. MCP-1 was increased in Kupffer cells (KCs) as …
Human Monoclonal Antibody Hcv1 Effectively Prevents And Treats Hcv Infection In Chimpanzees, Trevor J. Morin, Teresa J. Broering, Brett A. Leav, Barbara M. Blair, Kirk J. Rowley, Elisabeth N. Boucher, Yang Wang, Peter S. Cheslock, Michael Knauber, David B. Olsen, Steve W. Ludmerer, Gyongyi Szabo, Robert W. Finberg, Robert H. Purcell, Robert E. Lanford, Donna M. Ambrosino, Deborah C. Molrine, Gregory J. Babcock
Human Monoclonal Antibody Hcv1 Effectively Prevents And Treats Hcv Infection In Chimpanzees, Trevor J. Morin, Teresa J. Broering, Brett A. Leav, Barbara M. Blair, Kirk J. Rowley, Elisabeth N. Boucher, Yang Wang, Peter S. Cheslock, Michael Knauber, David B. Olsen, Steve W. Ludmerer, Gyongyi Szabo, Robert W. Finberg, Robert H. Purcell, Robert E. Lanford, Donna M. Ambrosino, Deborah C. Molrine, Gregory J. Babcock
Gyongyi Szabo
Hepatitis C virus (HCV) infection is a leading cause of liver transplantation and there is an urgent need to develop therapies to reduce rates of HCV infection of transplanted livers. Approved therapeutics for HCV are poorly tolerated and are of limited efficacy in this patient population. Human monoclonal antibody HCV1 recognizes a highly-conserved linear epitope of the HCV E2 envelope glycoprotein (amino acids 412-423) and neutralizes a broad range of HCV genotypes. In a chimpanzee model, a single dose of 250 mg/kg HCV1 delivered 30 minutes prior to infusion with genotype 1a H77 HCV provided complete protection from HCV infection, …
Cd81/Cd9 Tetraspanins Aid Plasmacytoid Dendritic Cells In Recognition Of Hcv-Infected Cells And Induction Of Ifnalpha, Shuye Zhang, Karen Kodys, Gregory Babcock, Gyongyi Szabo
Cd81/Cd9 Tetraspanins Aid Plasmacytoid Dendritic Cells In Recognition Of Hcv-Infected Cells And Induction Of Ifnalpha, Shuye Zhang, Karen Kodys, Gregory Babcock, Gyongyi Szabo
Gyongyi Szabo
Recognition of hepatitis C virus (HCV)-infected hepatocyes and interferon (IFN) induction are critical in antiviral immune response. We hypothesized that cell-cell contact between plasmacytoid dendritic cells (pDCs) and HCV-infected cells was required for IFNalpha induction via involvement of cell surface molecules. Co-culture of human peripheral blood mononuclear cells (PBMCs) with genotype 1a full length HCV genomic replicon cells (FL) or genotype 2a JFH-1 virus infected hepatoma cells (JFH-1), not with uninfected hepatoma cells (Huh7.5), induced IFNalpha production. Depletion of pDCs from PBMCs attenuated IFNalpha release and purified pDCs produced high levels of IFNalpha after co-culture with FL replicons or JFH-1 …
Il-1 Receptor Antagonist Ameliorates Inflammasome-Dependent Alcoholic Steatohepatitis In Mice, Jan Petrasek, Shashi Bala, Timea Csak, Dora Lippai, Karen Kodys, Victoria Menashy, Matthew Barrieau, So-Yun Min, Evelyn A. Kurt-Jones, Gyongyi Szabo
Il-1 Receptor Antagonist Ameliorates Inflammasome-Dependent Alcoholic Steatohepatitis In Mice, Jan Petrasek, Shashi Bala, Timea Csak, Dora Lippai, Karen Kodys, Victoria Menashy, Matthew Barrieau, So-Yun Min, Evelyn A. Kurt-Jones, Gyongyi Szabo
Gyongyi Szabo
Alcoholic liver disease (ALD) is characterized by steatosis and upregulation of proinflammatory cytokines, including IL-1beta. IL-1beta, type I IL-1 receptor (IL-1R1), and IL-1 receptor antagonist (IL-1Ra) are all important regulators of the IL-1 signaling complex, which plays a role in inflammation. Furthermore, IL-1beta maturation is dependent on caspase-1 (Casp-1). Using IL-1Ra-treated mice as well as 3 mouse models deficient in regulators of IL-1beta activation (Casp-1 and ASC) or signaling (IL-1R1), we found that IL-1beta signaling is required for the development of alcohol-induced liver steatosis, inflammation, and injury. Increased IL-1beta was due to upregulation of Casp-1 activity and inflammasome activation. The …