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Full-Text Articles in Life Sciences

Mitochondrial Antiviral Signaling Protein Defect Links Impaired Antiviral Response And Liver Injury In Steatohepatitis In Mice, Timea Csak, Angela Dolganiuc, Karen Kodys, Bharath Nath, Jan Petrasek, Shashi Bala, Dora Lippai, Gyongyi Szabo Oct 2012

Mitochondrial Antiviral Signaling Protein Defect Links Impaired Antiviral Response And Liver Injury In Steatohepatitis In Mice, Timea Csak, Angela Dolganiuc, Karen Kodys, Bharath Nath, Jan Petrasek, Shashi Bala, Dora Lippai, Gyongyi Szabo

Gyongyi Szabo

Mitochondrial dysfunction is a pathogenic feature of nonalcoholic steatohepatitis (NASH). NASH complicates hepatotropic viral disease. The mitochondrial antiviral signaling protein (MAVS) is the adapter of helicase receptors involved in sensing double-stranded RNA (dsRNA). We hypothesized that impaired MAVS function may contribute to insufficient antiviral response and liver damage in steatohepatitis. We identified reduced MAVS protein levels and increased MAVS association with the proteasome subunit alpha type 7 (PSMA7) in livers from mice given a methionine-choline-deficient (MCD) diet. Decreased association of MAVS with mitochondria and increased cytosolic cytochrome c indicated mitochondrial damage in steatohepatitis. In vivo administration of the synthetic dsRNA …


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 Oct 2012

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 …


Lipopolysaccharide Induces And Activates The Nalp3 Inflammasome In The Liver, Michal Ganz, Timea Csak, Bharath D. Nath, Gyongyi Szabo Oct 2012

Lipopolysaccharide Induces And Activates The Nalp3 Inflammasome In The Liver, Michal Ganz, Timea Csak, Bharath D. Nath, Gyongyi Szabo

Gyongyi Szabo

AIM: To examine the activation of the Nalp3 inflammasome and its downstream targets following lipopolysaccharide (LPS)-induced stimulation in the liver. METHODS: Six-to-eight-week-old C57BL/6 chow fed mice were injected intraperitoneally with 0.5 mug/g bodyweight LPS and sacrificed 2, 4, 6, 18 or 24 h later. LPS-induced liver damage was confirmed by a biochemical assay to detect alanine aminotransferase (ALT) levels. To determine if LPS stimulation in the liver led to activation of the inflammasome, real-time quantitative polymerase chain reaction was used to evaluate the mRNA expression of components of the Nalp3 inflammasome. Enzyme-linked immunosorbent assays were used to determine the protein …


Il-22 Signaling Contributes To West Nile Encephalitis Pathogenesis, Fengwei Bai, Penghua Wang, Lauren A. Zenewicz, Jianfeng Dai, David Gate, Gong Cheng, Long Yang, Feng Qian, Xiaoling Yuan, Ruth R. Montgomery, Richard A. Flavell, Terrence Town, Erol Fikrig Aug 2012

Il-22 Signaling Contributes To West Nile Encephalitis Pathogenesis, Fengwei Bai, Penghua Wang, Lauren A. Zenewicz, Jianfeng Dai, David Gate, Gong Cheng, Long Yang, Feng Qian, Xiaoling Yuan, Ruth R. Montgomery, Richard A. Flavell, Terrence Town, Erol Fikrig

Faculty Publications

The Th17 cytokine, IL-22, regulates host immune responses to extracellular pathogens. Whether IL-22 plays a role in viral infection, however, is poorly understood. We report here that Il22-/- mice were more resistant to lethal West Nile virus (WNV) encephalitis, but had similar viral loads in the periphery compared to wild type (WT) mice. Viral loads, leukocyte infiltrates, proinflammatory cytokines and apoptotic cells in the central nervous system (CNS) of Il22-/- mice were also strikingly reduced. Further examination showed that Cxcr2, a chemokine receptor that plays a non-redundant role in mediating neutrophil migration, was significantly reduced in Il22-/- …


Role Of Il-10 In The Immune Response To Staphylococcus Aureus Nasal Carriage, Teresa Fernandez Plaza May 2012

Role Of Il-10 In The Immune Response To Staphylococcus Aureus Nasal Carriage, Teresa Fernandez Plaza

Electronic Thesis and Dissertation Repository

Staphylococcus aureus is a human pathogen with the potential to cause life-threatening diseases, but it can also be found as a commensal in up to 50% of the population. Its main reservoir is located in the nostrils, where macrophages are the principal mucosal APC and elicit a predominantly IL-10 response. Induction of IL-10 requires phosohoinositide 3-kinase activity, upon stimulation with S. aureus ligands through toll-like receptor 2 binding. It is hypothesized that IL-10 production by macrophages in the nasal mucosa allows S. aureus to persist in this niche as a commensal. To test this hypothesis, a cohort of S. aureus …


Positive Emotions And Immune Respose To Influenza In Medically Stable Older Adults, Maryann J. Gierloff Jan 2012

Positive Emotions And Immune Respose To Influenza In Medically Stable Older Adults, Maryann J. Gierloff

Dissertations

Influenza results in substantial human suffering and health care costs. Evidence from psychoneuroimmunology suggests that emotions influence the immune system and may alter susceptibility to infectious diseases, like influenza. The purpose of this investigation was to evaluate the influence of psychological factors, health behaviors, circulating levels of proinflammatory cytokines and the development of influenza-like illness in older adults. Medically stable participants, 55 years of age and over, were enrolled from the general community and an elderly community. Psychological factors (emotions and perceived stress), health behaviors (sleep and physical activity) and plasma cytokine levels (IL-6 and IL-1B) were evaluated with respect …