Cell and Developmental Biology Commons^™

Lipocalin 2 Promotes The Establishment Of A Pro-Tumorigenic Microenvironment In Pancreatic Cancer, Sobeyda B. Gomez-Chou

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a disease characterized by a dismal prognosis with a 5-year survival rate of 7%. A unique hallmark of this disease is an abundant desmoplastic reaction that can account for up to 90% of the solid tumor volume. Key components of the PDAC stroma include the extracellular matrix (ECM) rich in collagen type I and III, activated pancreatic stellate cells (PSCs) and inflammatory cells such as neutrophils and macrophages. The main line of evidence has suggested a pro-tumorigenic role for the PDAC stroma as it has been shown to help enhance tumor growth, invasive potential and …

Sodium Channel Γenac Mediates Il-17 Synergized High Salt Induced Inflammatory Stress In Breast Cancer Cells, Suneetha Amara, Michael T. Ivy, Elbert L. Myles, Venkataswarup Tiriveedhi

Biology Faculty Research

Chronic inflammation is known to play a critical role in the development of cancer. Recent evidence suggests that high salt in the tissue microenvironment induces chronic inflammatory milieu. In this report, using three breast cancer-related cell lines, we determined the molecular basis of the potential synergistic inflammatory effect of sodium chloride (NaCl) with interleukin-17 (IL-17). Combined treatment of high NaCl (0.15M) with sub-effective IL-17 (0.1nM) induced enhanced growth in breast cancer cells along with activation of reactive nitrogen and oxygen (RNS/ROS) species known to promote cancer. Similar effect was not observed with equi-molar mannitol. This enhanced of ROS/RNS activity correlates …

Better Cognitive Control Of Emotional Information Is Associated With Reduced Pro-Inflammatory Cytokine Reactivity To Emotional Stress, Grant S. Shields, Shari Young Kuchenbecker, Sarah D. Pressman, Ken D. Sumida, George M. Slavich

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Stress is strongly associated with several mental and physical health problems that involve inflammation, including asthma, cardiovascular disease, certain types of cancer, and depression. It has been hypothesized that better cognitive control of emotional information may lead to reduced inflammatory reactivity to stress and thus better health, but to date no studies have examined whether differences in cognitive control predict pro-inflammatory cytokine responses to stress. To address this issue, we conducted a laboratory-based experimental study in which we randomly assigned healthy young-adult females to either an acute emotional stress (emotionally evocative video) or no-stress (control video) condition. Salivary levels of …

Resolution Of Inflammation Rescues Axon Initial Segment Disruption, Nicholas M. George

Theses and Dissertations

Axonal domains are required for proper neuron function. These domains are unstable and degenerate concurrent with the inflammation in multiple sclerosis (MS) and the inflammatory disease models experimental autoimmune encephalomyelitis (EAE) and lipopolysaccharide (LPS) induced inflammation. Previous studies from our laboratory have shown that the axon initial segment (AIS) is maintained independently of the presence of myelin, but that AIS disruption is seen in MS as well as EAE and LPS-mediated inflammation. AIS loss can be interrupted in the early stage of EAE using the anti-inflammatory drug Didox. However, the potential for Didox directed repair of the AIS in later …

Aspirin Triggered Resolution Phase Interaction Product D1: A Novel Treatment For Hyperoxic Acute Lung Injury, Ruan Rollin Cox, Jr.

USF Tampa Graduate Theses and Dissertations

Acute Lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS) are respiratory maladies that present immense clinical challenges. ALI affects 200,000 individuals annually and features a 40% mortality rate. ALI can be initiated by both pathogenic and sterile insults originating locally in the lungs or systemically. While immense research has been poured into this disease in an effort to find a therapeutic strategy, the heterogeneously diffuse nature of the disease has not yielded a cure for the disease. Death from this disease is strongly attributed to reduced gas exchange from a severely compromised alveolar-capillary barrier. The only …

Alternate Formulations For Optimization Of Plga Microsphere-Comprised Glucose Biosensor Coating Against Foreign Body Inflammation., Klair Lubonja

Honors Scholar Theses

In this study, dexamethasone loaded PLGA microsphere/PVA hydrogel composites were explored as an outer drug-eluting coating for implantable biosensors to provide defense against acute inflammation of the foreign body response. The microspheres, with a dexamethasone release target period of approximately two weeks, were manufactured under various conditions: different co-solvents and homogenization speeds. Particle size measurement, scanning electron microscopy and differential scanning calorimetry were performed for all the microsphere formulations prepared. The addition of acetone as a co-solvent for dexamethasone, at normal homogenization speeds, shows promise for the improvement of drug loading and the attainment of superior release profiles. PLGA microsphere/PVA …

Pharmaceutical Integrated Stress Response Enhancement Protects Oligodendrocytes And Provides A Potential Multiple Sclerosis Therapeutic., Sharon W Way, Joseph R Podojil, Benjamin L Clayton, Anita Zaremba, Tassie L Collins, Rejani B Kunjamma, Andrew P Robinson, Pedro Brugarolas, Robert H. Miller, Stephen D Miller, Brian Popko

Anatomy and Regenerative Biology Faculty Publications

Oligodendrocyte death contributes to the pathogenesis of the inflammatory demyelinating disease multiple sclerosis (MS). Nevertheless, current MS therapies are mainly immunomodulatory and have demonstrated limited ability to inhibit MS progression. Protection of oligodendrocytes is therefore a desirable strategy for alleviating disease. Here we demonstrate that enhancement of the integrated stress response using the FDA-approved drug guanabenz increases oligodendrocyte survival in culture and prevents hypomyelination in cerebellar explants in the presence of interferon-γ, a pro-inflammatory cytokine implicated in MS pathogenesis. In vivo, guanabenz treatment protects against oligodendrocyte loss caused by CNS-specific expression of interferon-γ. In a mouse model of MS, experimental …

The Role Of Alveolar Macrophages In Pulmonary Inflammation After Intoxication And Burn Injury, Jill Ann Shults

Dissertations

A positive blood alcohol concentration is detected in nearly half of burn patients admitted to the emergency room. The combined insult of being intoxicated at the time of burn injury results in more clinical complications, in comparison to non-intoxicated burn patients. Severe burn, with or without inhalation injury, is a common predisposing factor for the development of acute respiratory distress syndrome (ARDS). Exacerbated pulmonary inflammation and a net result of insufficient gas exchange underlie the large percentage of burn fatalities due to pulmonary complications. Previous studies in our laboratory indicate a drastic elevation in pulmonary inflammation in a mouse model …

The Gut-Liver Axis Regulates Pulmonary Inflammation After Intoxication And Burn Injury, Michael M. Chen

Dissertations

The increasing prevalence of binge drinking and its high association with traumatic injury warrant further investigation into the mechanisms underlying the worsened clinical outcomes associated with this combined injury. Existing literature suggests the liver is at the center of the postburn systemic response with crosstalk between the intestinal microbiome and the liver playing an important role after injury. There is a paucity in the literature, however, regarding the role of the gut-liver axis in the common clinical scenario of burns preceded by alcohol intoxication. Previous studies in our laboratory demonstrated intoxication potentiates postburn hepatic damage and IL-6 production in a …

Soy Isoflavones Mediate Radioprotection Of Normal Lung Tissue By Modulating The Radiation-Induced Inflammatory Response, Lisa Marie Abernathy

Wayne State University Dissertations

Radiation-induced lung injury (RILI) is caused by an early inflammatory process triggered by damage to lung parenchyma, epithelial cells, vascular endothelial cells and stroma. Initially, oxidative injuries after radiation induce altered expression of pro-inflammatory cytokines. Infiltrating inflammatory cells are stimulated and activated, producing additional mediators, resulting in a cytokine cascade. The expansion and perpetual activation of inflammatory cells, as well as lung parenchyma, lead to clinical pneumonitis. Activated cells produce molecular mediators and growth factors that affect the proliferation and gene expression of lung fibroblasts. This process leads to increased collagen synthesis and deposition, eventually leading to the development of …

Effects Of Acetyl Salicyclic Acid On Drosophila Models Of Cancer-Inflammation, Roma Rajwani

Dissertations and Theses

Chronic inflammation is a fundamental condition underlying many human disease pathologies including diabetes, cancer, and neurodegeneration. Indeed, one of the most commonly-used anti-inflammatory drugs, aspirin, has been shown to be effective in the treatment of many cancers. To understand the mechanistic linkages between inflammation and cancer, we used Drosophila models in which hyperactive immune signaling causes overproliferation of the hematopoietic system leading to the production of inflammatory blood tumors. In mutant animals, hematopoietic cells divide uncontrollably and exhibit pre-mature differentiation giving rise to large sticky cells. Some mutant cells infiltrate and adhere to cells of the fat body. The fat …

Immature Myeloid Cells Promote Tumor Formation Via Non-Suppressive Mechanism, Myrna Lillian Ortiz

USF Tampa Graduate Theses and Dissertations

ABSTRACT

Although there is ample evidence linking chronic inflammation with cancer, the cellular mechanisms involved in early events leading to tumor development remain unclear. Myeloid cells are an intricate part of inflammation. They consist of mature cells represented by macrophages, dendritic cells and granulocytes and a population of Immature Myeloid Cells (IMC), which in healthy individuals are cells in transition to mature cells. There is a substantial expansion of IMC in cancer and many other pathological conditions which is associated with pathologic activation of these cells. As a result, these cells acquire the ability to suppress immune responses and are …

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, …

The Effect Of Lactic Acid On Mast Cell Function, Andrew J. Spence

Theses and Dissertations

This study shows for the first time the effect that L-(+)-lactic acid has on mast cell activation. Lactic acid is a byproduct of anaerobic glycolysis and is associated with inflammatory environments such as wounds, tumors and, asthma. In this study, pre-treatment with lactic acid altered cytokine production by bone marrow-derived mast cells (BMMC). Specifically, lactic acid enhanced cytokine secretion following IgE cross-linking, but decreased IL-33 mediated cytokine production. These effects were altered by genetic background, since C57BL/6 mast cells demonstrated the aforementioned result, but lactic acid had no effect on IgE-mediated cytokine production in 129/SvJ mast cells. The affected cytokines …

Mechanisms Of Age-Related Inflammation And Cancer : The Synergistic Effect Of Oxidants And Calcium, Donald A. Mccarthy

Legacy Theses & Dissertations (2009 - 2024)

The accumulation of senescent cells during the process of aging has been implicated as causal in numerous age-related pathologies. Senescent cells adopt a secretory phenotype consisting of many factors including matrix remodeling enzymes, growth factors, cytokines, and chemokines. Their secretory nature is the primary reason that they are associated with disease, but it remains unclear why they become so inflammatory. Using primary human fibroblasts cultured to senescence, we mechanistically determined why senescent cells are such potent inducers of inflammation. Our findings indicate that the early production of the cytokine Interleukin 1-α (IL-1α) is central to this transition. We found that …

Effect Of Heme Oxygenase-1 On Matrix Metalloproteinase-3 Expression In Human Fibroblasts, Theresa A. Stangl

PCOM Biomedical Studies Student Scholarship

Heme oxygenase-1(HO-1) is an enzyme that plays a very important role in the resolution of inflammation. HO-1-based therapies are effective in a number of disease conditions. However, HO-1 also increases tumor growth, angiogenesis, metastasis and chemoresistance. Matrix metalloproteinase-3 (MMP-3) is an enzyme involved in physiological and pathophysiological tissue remodeling. Unbalanced expression of MMPs is a key feature of connective tissue destruction in chronic inflammatory conditions. Previously shown in this laboratory, the HO-1 inducer, hemin, increased MMP-3 mRNA expression in some HGF cultures. To assess whether HO-1 and/or its products regulate expression of MMP-3 in human fibroblasts, the effect of HO-1 …

Dietary Selenium Deficiency Exacerbates Dss-Induced Epithelial Injury And Aom/Dss-Induced Tumorigenesis., C. W. Barrett, K. Singh, A. K. Motley, M. K. Lintel, E. Matafonova, A. M. Bradley, W. Ning, Shenika Poindexter Toliver

Faculty and Staff Publications

Selenium (Se) is an essential micronutrient that exerts its functions via selenoproteins. Little is known about the role of Se in inflammatory bowel disease (IBD). Epidemiological studies have inversely correlated nutritional Se status with IBD severity and colon cancer risk. Moreover, molecular studies have revealed that Se deficiency activates WNT signaling, a pathway essential to intestinal stem cell programs and pivotal to injury recovery processes in IBD that is also activated in inflammatory neoplastic transformation. In order to better understand the role of Se in epithelial injury and tumorigenesis resulting from inflammatory stimuli, we examined colonic phenotypes in Se-deficient or …

Endotoxin-Induced Inflammation & Morphine-Induced Conditioned Place Preference In The Hiv-1 Transgenic Rat, Natasha F. Homji-Mishra

Seton Hall University Dissertations and Theses (ETDs)

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Higher Il-6 And Il6:Igf Ratio In Patients With Barth Syndrome, Lori D. Wilson, Sadeeka Al-Majid, Cyril Rakovski, Christina D. Schwindt

Mathematics, Physics, and Computer Science Faculty Articles and Research

Background: Barth Syndrome (BTHS) is a serious X-linked genetic disorder associated with mutations in the tafazzin gene (TAZ, also called G4.5). The multi-system disorder is primarily characterized by the following pathologies: cardiac and skeletal myopathies, neutropenia, growth delay, and exercise intolerance. Although growth anomalies have been widely reported in BTHS, there is a paucity of research on the role of inflammation and the potential link to alterations in growth factors levels in BTHS patients.

Methods: Plasma from 36 subjects, 22 patients with Barth Syndrome (0.5 - 24 yrs) and 14 healthy control males (8 - 21 yrs) was …

Evidence Of A Neurogenic Component During Ige-Mediated Inflammation In Murine Skin, Victoria Jean Cavanaugh

Biological Sciences Theses & Dissertations

The direct stimulation of sensory nerves or the intradermal injection of neuropeptides triggers a cutaneous inflammatory response that involves the degranulation of mast cells. These neurogenic inflammatory reactions are physiologically similar to IgE-mediated hypersensitivity responses, which also depend on mast cells. Although non-antigenic stimuli distinguish neurogenic from IgE-mediated inflammation, the similarity of their effector stages suggested that peripheral nerves may also participate in lgE-mediated responses. To examine this hypothesis, IgE responses were elicited in denervated skin. A murine model was developed where the footpad was denervated by surgically removing a 2 mm segment of the sciatic nerve, proximal to the …

Phasic Response Of Peripheral Nerves To Inflammation, Ralph Lee Myers

University of the Pacific Theses and Dissertations

Acute inflammation is associated with injury to tissues, whether it be from mechanical destruction, or from the introduction of a noxious substance into the tissue. Inflammation is a homeostatic process, adapted to neutralize harmful substances and restore injured tissue. Celsus (c. A.D. 178) provided the first documented characterization of inflammation. He recognized redness, heat, swelling and pain as the cardinal signs of the inflammatory reaction. Loss of function was later added to this list of symptons (Movat. 1971).