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Articles 1 - 30 of 47
Full-Text Articles in Immunology and Infectious Disease
Cytokine Data For Cytokine Profile Assessment From Peruvian Pinniped (Arctocephalus Australis And Otaria Byronia) Plasma, Mykenzee Munaco, Milton Levin, Michael Adkesson, Susana Cárdenas-Alayzad, Dimitrios G. Giarikos, Amy C. Hirons
Cytokine Data For Cytokine Profile Assessment From Peruvian Pinniped (Arctocephalus Australis And Otaria Byronia) Plasma, Mykenzee Munaco, Milton Levin, Michael Adkesson, Susana Cárdenas-Alayzad, Dimitrios G. Giarikos, Amy C. Hirons
SECLER Data
Large colonies of two vulnerable, sympatric pinniped species, Peruvian fur seals (Arctocephalus australis Peruvian subpopulation; PFS) and South American sea lions (Otaria byronia; SASL), reside and reproduce in Punta San Juan, Peru (PSJ) where they are exposed to stressors such as contaminants and El Niño Southern Oscillation (ENSO) events. The use of cytokines as immune biomarkers can be indicative of an animal’s health and function by allowing for the assessment of an individual's cytokine balance as type I helper T cells (Th1) or type II helper T cells (Th2) dominant. Utilizing archived pinniped plasma samples from 2009-2019 …
Cytokine Profiles In Peruvian Pinnipeds And Their Relationships With Environmental Stressors, Mykenzee L. Munaco
Cytokine Profiles In Peruvian Pinnipeds And Their Relationships With Environmental Stressors, Mykenzee L. Munaco
All HCAS Student Capstones, Theses, and Dissertations
Large colonies of two vulnerable, sympatric pinniped species, Peruvian fur seals (Arctocephalus australis Peruvian subpopulation; PFS) and South American sea lions (Otaria byronia; SASL), reside and reproduce in Punta San Juan, Peru (PSJ) where they are exposed to stressors such as environmental contaminants and El Niño-Southern Oscillation (ENSO) events. Cytokine concentrations can be indicative of an animal’s health and immune function by allowing for immunoresponse characterization as Th1 or Th2 dominant. Utilizing an archived pinniped plasma collection of samples from 2009-2019 (n=148), 13 cytokines were analyzed in PFS and SASL: GM-CSF, IFN-γ, KC-like, MCP-1, TNF-α, IL-2, IL-6, …
Interrogation Of The Inkt-Mait Cell Interface, Nicole I. Wang
Interrogation Of The Inkt-Mait Cell Interface, Nicole I. Wang
Undergraduate Student Research Internships Conference
Invariant natural killer T (iNKT) cells and mucosa-associated invariant T (MAIT) cells are unique subsets of invariant T cells that are involved in regulating various tumor responses and display potent anti-microbial properties. Upon their activation, iNKT and MAIT cells secrete large quantities of T helper 1 (Th1)-, Th2-, and Th17-type cytokines that mediate their ability to regulate a variety of other immune cells, including B cells, natural killer cells, and macrophages. However, whether and how iNKT and MAIT cells regulate each other in vivo remains unknown. Here, we provide evidence for a cross-talk between iNKT and MAIT cells that resembles …
Cancer Salt Nostalgia, Aashish S. Allu, Venkataswarup Tiriveedhi
Cancer Salt Nostalgia, Aashish S. Allu, Venkataswarup Tiriveedhi
Biology Faculty Research
High-salt (sodium chloride) diets have been strongly associated with disease states and poor health outcomes. Traditionally, the impact of salt intake is primarily studied in cardiovascular diseases, hypertension and renal diseases; however, recently there has been increasing evidence demonstrating the role of salt in autoimmune diseases. Salt has been shown to modulate the inflammatory activation of immune cells leading to chronic inflammation-related ailments. To date, there is minimal evidence showing a direct correlation of salt with cancer incidence and/or cancer-related adverse clinical outcomes. In this review article, we will discuss the recent understanding of the molecular role of salt, and …
The Impacts Of Psychological Stress On Innate-Like Invariant T Cell Survival, Phenotype, And Function, Patrick Rudak
The Impacts Of Psychological Stress On Innate-Like Invariant T Cell Survival, Phenotype, And Function, Patrick Rudak
Electronic Thesis and Dissertation Repository
The nervous system serves numerous critical roles in the regulation of immune responses. Consequently, psychological stress can result in immunosuppressive states that are conducive to the development of infection and cancer. Yet, whether stress impacts the functions of innate-like T lymphocytes including invariant natural killer T (iNKT) and mucosa-associated invariant T (MAIT) cells, which participate in early host defense against pathogens and tumors, remains poorly understood. In this thesis, I leveraged multiple established methods with which to induce psychological stress in mice. I demonstrate that TH1- and TH2-type immune responses initiated by iNKT …
Placenta-Expanded Stromal Cell Therapy In A Rodent Model Of Simulated Weightlessness, Amber M. Paul, Linda Rubinstein, Charles Houseman, Metadel Abegaz, Steffy Tabares Ruiz
Placenta-Expanded Stromal Cell Therapy In A Rodent Model Of Simulated Weightlessness, Amber M. Paul, Linda Rubinstein, Charles Houseman, Metadel Abegaz, Steffy Tabares Ruiz
Publications
Long duration spaceflight poses potential health risks to astronauts during flight and re-adaptation after return to Earth. There is an emerging need for NASA to provide successful and reliable therapeutics for long duration missions when capability for medical intervention will be limited. Clinically relevant, human placenta-derived therapeutic stromal cells (PLX-PAD) are a promising therapeutic alternative. We found that treatment of adult female mice with PLX-PAD near the onset of simulated weightlessness by hindlimb unloading (HU, 30 d) was well-tolerated and partially mitigated decrements caused by HU. Specifically, PLX-PAD treatment rescued HU-induced thymic atrophy, and mitigated HU-induced changes in percentages of …
The Effect Of Age On Neurological Inflammation To Acute Sleep Fragmentation In Mice, Molly Taylor
The Effect Of Age On Neurological Inflammation To Acute Sleep Fragmentation In Mice, Molly Taylor
Mahurin Honors College Capstone Experience/Thesis Projects
Obstructive sleep apnea is identified by recurring events of airway collapse during sleep, intermittent hypoxia, and perturbations in sleep continuity, known as sleep fragmentation. There is evidence to suggest that elderly patients are more at risk of developing obstructive sleep apnea. The purpose of this study was to assess whether age affects neurological inflammatory responses to acute sleep fragmentation. This assessment was made by subjecting young (4-5 months old) and old (10-11 months old) male C57BL/6j mice to automated sleep fragmentation, as well as having mice in both age categories as a control with no sleep fragmentation, for twenty-four hours. …
Morphological Changes In Dorsal Root Ganglia Macrophages Associated With Neuropathic Pain Mechanisms Suggest A Novel Target For Chronic Pain Therapy, Emily Kussick
CMC Senior Theses
The present study examined morphological changes in the dorsal root ganglia (DRG) following an innate immune stimulus. The importance of the DRG has increasingly become recognized in pain processing as more than just the home of primary afferent cell bodies. All sensory information passes through the DRG via the primary afferents, and on to the spinal cord. The primary afferents synapse with second-order neurons in the spinal cord that ascend towards the brain, where they transmit the pain signal to the limbic forebrain and/or the somatosensory cortex for processing. The DRG is an interesting niche to study at as it …
Dendritic Cell Development And Function, Vivek Durai
Dendritic Cell Development And Function, Vivek Durai
Arts & Sciences Electronic Theses and Dissertations
Dendritic cells (DCs) are a group of immune cells that include both classical dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs). cDCs are further comprised of two distinct subsets, cDC1s and cDC2s, which play critical roles in the initiation of innate and adaptive immune responses. Understanding how these lineages develop and function is therefore paramount. All DCs require the receptor tyrosine kinase Flt3 and its ligand Flt3L for their development, but the loss of Flt3L in mice leads to a more severe DC deficiency than does the loss of Flt3. This has led to speculation that Flt3L can bind to …
Tobacco Enhances Bacterial-Induced Periodontal Bone Loss In Mice., Mina Iskander
Tobacco Enhances Bacterial-Induced Periodontal Bone Loss In Mice., Mina Iskander
Electronic Theses and Dissertations
Background: Tobacco smoking is the leading environmental risk factor for periodontal diseases. Delineation of the mechanisms underlying tobacco-induced or exacerbated periodontitis is hampered by the lack of an appropriate and reliable animal model. Hypothesis: We hypothesized that Porphyromonas-gingivalis-infected, cigarette smoke-exposed mice would represent reproducible models of acute (ligature model) and chronic (oral gavage model) tobacco-enhanced periodontitis that reflect multiple aspects of the disease noted in human smokers. Methods: In a chronic oral gavage disease model, Balb/c mice (6-8 weeks, 4 groups of n = 6 per group) were exposed to smoke produced by a Teague-10 smoking machine from 1R6F research …
Tumor Necrosis Factor-Alpha Signaling May Contribute To Chronic West Nile Virus Post-Infectious Proinflammatory State, A. Arturo Leis, Marie F. Grill, Brent P. Goodman, Syed B. Sadiq, David J. Sinclair, Parminder J.S. Vig, Fengwei Bai
Tumor Necrosis Factor-Alpha Signaling May Contribute To Chronic West Nile Virus Post-Infectious Proinflammatory State, A. Arturo Leis, Marie F. Grill, Brent P. Goodman, Syed B. Sadiq, David J. Sinclair, Parminder J.S. Vig, Fengwei Bai
Faculty Publications
Background: West Nile virus (WNV) causes a spectrum of human disease ranging from a febrile illness (WNV fever) to severe neuroinvasive disease (meningitis, encephalitis, acute flaccid paralysis). Since WNV gained entry into North America in 1999, clinicians caring for WNV survivors have observed persistent neurological symptoms occurring long-after the production of neutralizing antibodies and clearance of the virus. Accordingly, alternative pathogeneses other than direct viral invasion have been hypothesized to explain these post-infectious symptoms. The dominant hypothesis is that antiviral inflammatory responses triggered initially to clear WNV may persist to promote a post-infectious proinflammatory state.
Methods: In 4 serologically-confirmed …
Effects Of Alpha- And Beta-Adrenergic Receptor Blockade Upon Inflammatory Responses To Acute And Chronic Sleep Fragmentation, Nicholas David Wheeler
Effects Of Alpha- And Beta-Adrenergic Receptor Blockade Upon Inflammatory Responses To Acute And Chronic Sleep Fragmentation, Nicholas David Wheeler
Masters Theses & Specialist Projects
Generally, sleep is viewed as a recuperative process and its dysregulation has
cognitive, metabolic, immunological, and inflammatory implications that are largely deleterious to human health. Epidemiological and empirical studies have suggested that sleep fragmentation (SF) as result of obstructive sleep apnea (OSA) and other sleep abnormalities leads to pronounced systemic inflammatory responses, which are influenced by the sympathetic nervous system (SNS). However, the underlying molecular mechanisms contributing to SNS regulation of SF-induced inflammatory states are not fully understood. To assess the effects of the SNS system, C57BL/6j female mice were placed in automated SF chambers (12L:12D) and subjected to either …
Defective Transcriptional Programming Of Effector Cd8 T Cells In Aged Mice Is Cell-Extrinsic And Can Be Corrected By Administration Of Il-12 And Il-18, Mladen Jergovic, Heather L. Thompson, Kristin R. Renkema, Megan J. Smithey, Janko Nikolich-Zugich
Defective Transcriptional Programming Of Effector Cd8 T Cells In Aged Mice Is Cell-Extrinsic And Can Be Corrected By Administration Of Il-12 And Il-18, Mladen Jergovic, Heather L. Thompson, Kristin R. Renkema, Megan J. Smithey, Janko Nikolich-Zugich
Peer Reviewed Articles
In response to infection with intracellular microorganisms, old mice mobilize decreased numbers of antigen-specific CD8 T cells with reduced expression of effector molecules and impaired cytolytic activity. Molecular mechanisms behind these defects and the cell-intrinsic (affecting naïve CD8 T cells themselves) vs. extrinsic, microenvironmental origin of such defects remain unclear. Using reciprocal transfer experiments of highly purified naïve T cells from adult and old transgenic OT-1 mice, we decisively show that the dominant effect is cell-extrinsic. Naïve adult OT-1 T cells failed to expand and terminally differentiate in the old organism infected with Listeria-OVA. This defect was preceded by …
Natural Autoantibodies: Origin, Function And Utility For Diagnosis Of Disease, Abhirup Sarkar
Natural Autoantibodies: Origin, Function And Utility For Diagnosis Of Disease, Abhirup Sarkar
Graduate School of Biomedical Sciences Theses and Dissertations
Autoantibodies (aAbs) by the simplest definitions have been described as antibodies against self-antigens and were exclusively associated with autoimmune diseases. Eventually, studies demonstrated that they are abundant in the blood of all human sera, regardless of age, gender, or the presence or absence of disease, and were thus named as ‘natural autoantibodies’. The underlying reason for their ubiquity has remained elusive, but we have hypothesized that they are responsible for clearing blood-borne cell and tissue debris generated under conditions of health and disease. To test this, we chose to use two widely different disease model systems, namely neurodegenerative diseases and …
Leukemia Inhibitory Factor Modulates The Peripheral Immune Response In A Rat Model Of Emergent Large Vessel Occlusion, Stephanie M. Davis, Lisa A. Collier, Edric D. Winford, Christopher C. Leonardo, Craig T. Ajmo Jr., Elspeth A. Foran, Timothy J. Kopper, John C. Gensel, Keith R. Pennypacker
Leukemia Inhibitory Factor Modulates The Peripheral Immune Response In A Rat Model Of Emergent Large Vessel Occlusion, Stephanie M. Davis, Lisa A. Collier, Edric D. Winford, Christopher C. Leonardo, Craig T. Ajmo Jr., Elspeth A. Foran, Timothy J. Kopper, John C. Gensel, Keith R. Pennypacker
Neurology Faculty Publications
Background: The migration of peripheral immune cells and splenocytes to the ischemic brain is one of the major causes of delayed neuroinflammation after permanent large vessel stroke. Other groups have demonstrated that leukemia inhibitory factor (LIF), a cytokine that promotes neural cell survival through upregulation of antioxidant enzymes, promotes an anti-inflammatory phenotype in several types of immune cells. The goal of this study was to determine whether LIF treatment modulates the peripheral immune response after stroke.
Methods: Young male (3 month) Sprague-Dawley rats underwent sham surgery or permanent middle cerebral artery occlusion (MCAO). Animals were administered LIF (125 μg/kg) or …
The Trophic Life Cycle Stage Of The Opportunistic Fungal Pathogen Pneumocystis Murina Hinders The Ability Of Dendritic Cells To Stimulate Cd4+ T Cell Responses, Heather M. Evans, Andrew Simpson, Shu Shen, Arnold J. Stromberg, Carol L. Pickett, Beth A. Garvy
The Trophic Life Cycle Stage Of The Opportunistic Fungal Pathogen Pneumocystis Murina Hinders The Ability Of Dendritic Cells To Stimulate Cd4+ T Cell Responses, Heather M. Evans, Andrew Simpson, Shu Shen, Arnold J. Stromberg, Carol L. Pickett, Beth A. Garvy
Microbiology, Immunology, and Molecular Genetics Faculty Publications
The life cycle of the opportunistic fungal pathogen Pneumocystis murina consists of a trophic stage and an ascus-like cystic stage. Infection with the cyst stage induces proinflammatory immune responses, while trophic forms suppress the cytokine response to multiple pathogen-associated molecular patterns (PAMPs), including β-glucan. A targeted gene expression assay was used to evaluate the dendritic cell response following stimulation with trophic forms alone, with a normal mixture of trophic forms and cysts, or with β-glucan. We demonstrate that stimulation with trophic forms downregulated the expression of multiple genes normally associated with the response to infection, including genes encoding …
Peripheral Administration Of The Soluble Tnf Inhibitor Xpro1595 Modifies Brain Immune Cell Profiles, Decreases Beta-Amyloid Plaque Load, And Rescues Impaired Long-Term Potentiation In 5xfad Mice, Kathryn P. Macpherson, Pradoldej Sompol, George T. Kannarkat, Jianjun Chang, Lindsey Sniffen, Mary E. Wildner, Christopher M. Norris, Malú G. Tansey
Peripheral Administration Of The Soluble Tnf Inhibitor Xpro1595 Modifies Brain Immune Cell Profiles, Decreases Beta-Amyloid Plaque Load, And Rescues Impaired Long-Term Potentiation In 5xfad Mice, Kathryn P. Macpherson, Pradoldej Sompol, George T. Kannarkat, Jianjun Chang, Lindsey Sniffen, Mary E. Wildner, Christopher M. Norris, Malú G. Tansey
Sanders-Brown Center on Aging Faculty Publications
Clinical and animal model studies have implicated inflammation and peripheral immune cell responses in the pathophysiology of Alzheimer’s disease (AD). Peripheral immune cells including T cells circulate in the cerebrospinal fluid (CSF) of healthy adults and are found in the brains of AD patients and AD rodent models. Blocking entry of peripheral macrophages into the CNS was reported to increase amyloid burden in an AD mouse model. To assess inflammation in the 5xFAD (Tg) mouse model, we first quantified central and immune cell profiles in the deep cervical lymph nodes and spleen. In the brains of Tg mice, activated (MHCII …
The Five Immune Forces Impacting Dna-Based Cancer Immunotherapeutic Strategy, Suneetha Amara, Venkataswarup Tiriveedhi
The Five Immune Forces Impacting Dna-Based Cancer Immunotherapeutic Strategy, Suneetha Amara, Venkataswarup Tiriveedhi
Biology Faculty Research
DNA-based vaccine strategy is increasingly realized as a viable cancer treatment approach. Strategies to enhance immunogenicity utilizing tumor associated antigens have been investigated in several pre-clinical and clinical studies. The promising outcomes of these studies have suggested that DNA-based vaccines induce potent T-cell effector responses and at the same time cause only minimal side-effects to cancer patients. However, the immune evasive tumor microenvironment is still an important hindrance to a long-term vaccine success. Several options are currently under various stages of study to overcome immune inhibitory effect in tumor microenvironment. Some of these approaches include, but are not limited to, …
Immune Responses In Hibernating Little Brown Myotis (Myotis Lucifugus) With White-Nose Syndrome, Thomas M. Lilley, Jenni M. Prokkola, Elisabeth Jeanine Rogers, Sarah Gronsky, Allen Kurta, Deeann Reeder, Kenneth A. Field
Immune Responses In Hibernating Little Brown Myotis (Myotis Lucifugus) With White-Nose Syndrome, Thomas M. Lilley, Jenni M. Prokkola, Elisabeth Jeanine Rogers, Sarah Gronsky, Allen Kurta, Deeann Reeder, Kenneth A. Field
Faculty Journal Articles
White-nose syndrome (WNS) is a fungal disease responsible for decimating many bat populations in North America. Pseudogymnoascus destructans (Pd), the psychrophilic fungus responsible for WNS, prospers in the winter habitat of many hibernating bat species. The immune response that Pd elicits in bats is not yet fully understood; antibodies are produced in response to infection by Pd, but they may not be protective and indeed may be harmful. To understand how bats respond to infection during hibernation, we studied the effect of Pd inoculation on the survival and gene expression of captive hibernating Myotis lucifugus with varying …
Development Of Cellular Assays To Monitor Enzymatic And Biological Activity Of Cd73: A Key Modulator Of Anti-Tumor Immune Response, Alexandra Fanuka
Development Of Cellular Assays To Monitor Enzymatic And Biological Activity Of Cd73: A Key Modulator Of Anti-Tumor Immune Response, Alexandra Fanuka
Graduate School of Biomedical Sciences Theses and Dissertations
Ecto-5’-nucleotidase, known as CD73, is an extracellular enzyme that converts adenosine monophosphate (AMP) to adenosine and has recently been identified as a potential drug target for cancer immunotherapy. Its immunosuppressive effects, mediated by the activity of adenosine, are associated with higher rates of tumor invasion and metastasis, as well as poorer prognoses overall in many cancer types. CD73 is often co-expressed with ectonucleoside triphosphate diphosphohydrolase-1 (CD39), which catalyzes the conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP), and ADP to AMP on the surface of tumor cells. Dual expression further propagates immunosuppressive effects of adenosine in the tumor microenvironment. …
Lipophosphoglycans From Leishmania Amazonensis Strains Display Immunomodulatory Properties Via Tlr4 And Do Not Affect Sand Fly Infection, Paula M. Nogueira, Rafael R. Assis, Ana C. Torrecilhas, Elvira M. Saraiva, Natália L. Pessoa, Marco A. Campos, Eric F. Marialva, Cláudia M. Ríos-Velasquez, Felipe A. Pessoa, Nágila F. Secundino, Jerônimo N. Rugani, Elsa Nieves, Salvatore J. Turco, Maria N. Melo, Rodrigo P. Soares
Lipophosphoglycans From Leishmania Amazonensis Strains Display Immunomodulatory Properties Via Tlr4 And Do Not Affect Sand Fly Infection, Paula M. Nogueira, Rafael R. Assis, Ana C. Torrecilhas, Elvira M. Saraiva, Natália L. Pessoa, Marco A. Campos, Eric F. Marialva, Cláudia M. Ríos-Velasquez, Felipe A. Pessoa, Nágila F. Secundino, Jerônimo N. Rugani, Elsa Nieves, Salvatore J. Turco, Maria N. Melo, Rodrigo P. Soares
Molecular and Cellular Biochemistry Faculty Publications
The immunomodulatory properties of lipophosphoglycans (LPG) from New World species of Leishmania have been assessed in Leishmania infantum and Leishmania braziliensis, the causative agents of visceral and cutaneous leishmaniasis, respectively. This glycoconjugate is highly polymorphic among species with variation in sugars that branch off the conserved Gal(β1,4)Man(α1)-PO4 backbone of repeat units. Here, the immunomodulatory activity of LPGs from Leishmania amazonensis, the causative agent of diffuse cutaneous leishmaniasis, was evaluated in two strains from Brazil. One strain (PH8) was originally isolated from the sand fly and the other (Josefa) was isolated from a human case. The ability of …
Granulocyte Colony-Stimulating Factor: Its Role In Gut-Homing Macrophage Generation And Colitis, And Production By Probiotics, Shahab Meshkibaf
Granulocyte Colony-Stimulating Factor: Its Role In Gut-Homing Macrophage Generation And Colitis, And Production By Probiotics, Shahab Meshkibaf
Electronic Thesis and Dissertation Repository
The pleiotropic cytokine granulocyte-colony stimulatory factor (G-CSF) is mainly required for the generation of neutrophils, but its role in macrophage generation has also been reported. In addition, G-CSF is effective for the down-regulation of inflammatory cytokines and ameliorating gut disorders, such as colitis. However, the G-CSF function in macrophage generation and gut immunity remains unclear. The first focus of this thesis was to assess the role of G-CSF in macrophage generation and its contribution to gut immunity. G-CSF was found to promote the generation of Gr-1high/F4/80+ macrophages in macrophage (M)-CSF-treated bone marrow cells, most likely through suppressing cell death. Gr-1high …
Critical Roles For Interleukin 1 And Tumor Necrosis Factor Alpha In Antibody-Induced Arthritis, Hong Ji, Allison Pettit, Koichiro Ohmura, Adriana Ortiz-Lopez, Veronique Duchatelle, Claude Degott, Ellen M. Gravallese, Diane Mathis, Christophe Benoist
Critical Roles For Interleukin 1 And Tumor Necrosis Factor Alpha In Antibody-Induced Arthritis, Hong Ji, Allison Pettit, Koichiro Ohmura, Adriana Ortiz-Lopez, Veronique Duchatelle, Claude Degott, Ellen M. Gravallese, Diane Mathis, Christophe Benoist
Ellen M. Gravallese
In spontaneous inflammatory arthritis of K/BxN T cell receptor transgenic mice, the effector phase of the disease is provoked by binding of immunoglobulins (Igs) to joint surfaces. Inflammatory cytokines are known to be involved in human inflammatory arthritis, in particular rheumatoid arthritis, although, overall, the pathogenetic mechanisms of the human affliction remain unclear. To explore the analogy between the K/BxN model and human patients, we assessed the role and relative importance of inflammatory cytokines in K/BxN joint inflammation by transferring arthritogenic serum into a panel of genetically deficient recipients. Interleukin (IL)-1 proved absolutely necessary. Tumor necrosis factor (TNF)-alpha was also …
Toll-Like Receptors In Liver Disease, Jan Petrasek, Timea Csak, Gyongyi Szabo
Toll-Like Receptors In Liver Disease, Jan Petrasek, Timea Csak, Gyongyi Szabo
Gyongyi Szabo
Activation of inflammatory signaling pathways is of central importance in the pathogenesis of alcoholic liver disease (ALD) and nonalcoholic steatohepatitis (NASH). Recent studies demonstrated that Toll-like receptors, the sensors of microbial and endogenous danger signals, are expressed and activated in innate immune cells as well as in parenchymal cells in the liver and thereby contribute to ALD and NASH. In this review, we emphasize the importance of gut-derived endotoxin and its recognition by TLR4 in the liver. The significance of TLR-induced intracellular signaling pathways and cytokine production as well as the contribution of individual cell types to the inflammation is …
Use Of Cholera Toxin B As A Vaccine Adjuvant Activates Antigen Presenting Cells And Stimulates Production Of Pro-Inflammatory Cytokines, Heather C. Romlein
Use Of Cholera Toxin B As A Vaccine Adjuvant Activates Antigen Presenting Cells And Stimulates Production Of Pro-Inflammatory Cytokines, Heather C. Romlein
Seton Hall University Dissertations and Theses (ETDs)
Francisella tularensis is an intracellular pathogen that has been classified as a category “A” bioterrorism agent by the Centers For Disease Control. To date, there is no approved vaccine to provide protection against this pathogen. Previous in vivo studies with mice have shown that a mucosally targeted vaccine preparation of inactivated F. tularensis (iFt) adjuvanted with Cholera toxin “B” (CTB), successfully granted full protection against a less virulent strain (FT LVS) of the bacterium and provided partial protection against a more virulent strain (SchuS4). However, the mechanisms of this protection are not fully understood. In this …
Tethered Il-15 To Augment The Therapeutic Potential Of T Cells Expressing Chimeric Antigen Receptor: Maintaining Memory Potential, Persistence, And Antitumor Activity, Lenka Hurton
Dissertations & Theses (Open Access)
Tethered IL-15 to augment the therapeutic potential of T cells expressing chimeric antigen receptor: Maintaining memory potential, persistence, and antitumor activity
Adoptive immunotherapy can retarget T cells to CD19, a tumor-associated antigen (TAA) expressed on B-cell malignancies, by the expression of a chimeric antigen receptor (CAR). Infusion of CAR-modified T cells for the treatment B-cell malignancies has demonstrated promise in preclinical and clinical trials. These data highlight the ability of infused CD19-specific T cells to be synchronously activated by large burdens of CD19+ leukemia and lymphoma. This can lead to dramatic antitumor effects, but also exposes the recipient to …
Blockade Of Mast Cell Activation Reduces Cutaneous Scar Formation, Lin Chen, Megan Schrementi, Matthew J. Ranzer, Traci A. Wilgus, Luisa A. Dipietro
Blockade Of Mast Cell Activation Reduces Cutaneous Scar Formation, Lin Chen, Megan Schrementi, Matthew J. Ranzer, Traci A. Wilgus, Luisa A. Dipietro
Faculty Publications & Research
Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair, …
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
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
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
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 …