Open Access. Powered by Scholars. Published by Universities.®

Digital Commons Network

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 8 of 8

Full-Text Articles in Entire DC Network

Transcription Regulation Of Human Il1b Gene In Monocytes And Lymphoid Cd4 T Cells, Sree H. Pulugulla Dec 2019

Transcription Regulation Of Human Il1b Gene In Monocytes And Lymphoid Cd4 T Cells, Sree H. Pulugulla

Electronic Theses and Dissertations

Cytokines are key regulators of the inflammatory response and play an important role in facilitating intercellular communication between various immune cell types. Interleukin‑1β (IL‑1β) is a potent pro-inflammatory cytokine that is required for robust initiation of innate immune response and subsequent development of adaptive immunity. IL-1β is first synthesized as an inactive cytoplasmic, non‑glycosylated, precursor molecule (proIL‑1β) by monocytes and macrophages in response to invading pathogenic microbes. The activation of caspase‑1 by inflammasomes cleaves proIL-1β into mature biologically active IL-1β that is released from cells via a non-classical, endoplasmic reticulum‑independent secretory pathway directly from the cytoplasm via Gasdermin D membrane …


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 Sep 2019

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 …


Brain-Specific And Systemic Inflammatory Response Following Repetitive Concussive Impact In A Mouse Model, So Young Eo Jul 2019

Brain-Specific And Systemic Inflammatory Response Following Repetitive Concussive Impact In A Mouse Model, So Young Eo

Electronic Thesis and Dissertation Repository

Concussion is the most common form of mild traumatic brain injury (mTBI). TBI resolution is modulated by neuroinflammation, which is augmented by the infiltration of innate immune cells from the circulation. Peripheral, myeloid immune cells not only invade neural tissues but other organs as well causing local inflammation and tissue damage, known as systemic inflammatory response syndrome. Here, I assessed the temporal and anatomical nature of the neural and systemic cellular inflammatory response to repetitive, mTBI in a 3-hit mouse model of concussion. The results showed significant microglial activity, accumulation of peripheral myeloid cells and prominent axonal damage post-injury. The …


The Cxcr2-Dependent Role Of Cancer-Associated Fibroblasts In Pancreatic Ductal Adenocarcinoma, Mohammad Awaji May 2019

The Cxcr2-Dependent Role Of Cancer-Associated Fibroblasts In Pancreatic Ductal Adenocarcinoma, Mohammad Awaji

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, the fourth leading cause of cancer-related deaths in the USA with over 40,000 deaths per year. Unlike other major cancer types, the progress in dealing with PDAC is plodding, attributed mainly to the asymptomatic nature of the disease, the late diagnosis and the ineffectiveness of current therapies. A better understanding of the biology of the disease could permit the discovery of novel diagnostic and therapeutic tools. With that in mind, we present this dissertation that investigates the tumor-stromal interaction underlined by genetic alterations and inflammation. PDAC develop as …


Binge Alcohol Drinking Exacerbates Ulcerative Colitis Flare, Abigail Cannon Jan 2019

Binge Alcohol Drinking Exacerbates Ulcerative Colitis Flare, Abigail Cannon

Dissertations

Inflammatory Bowel Disease (IBD) remains a prominent medical concern affecting over 1.4 million people in the U.S. One of the most common forms of the disease is ulcerative colitis (UC), and UC patients will often head doctor's advice to refrain from drinking alcohol. However, whether this phenomenon of alcohol exacerbating UC symptoms occurs is still unknown, which necessitated the generation of a mouse model of UC and binge alcohol. Therefore, we examined a range of DSS concentrations (2-4%) and 2 alcohol paradigms in C57BL/6 mice. Mice receiving 2% DSS ad libitum for five days with a three-day alcohol binge had …


Protection From Staphylococcus Aureus Bloodstream Infection By Probiotic Exopolysaccharide, Wonbeom Paik Jan 2019

Protection From Staphylococcus Aureus Bloodstream Infection By Probiotic Exopolysaccharide, Wonbeom Paik

Dissertations

Staphylococcus aureus is known to cause severe systemic infection with high mortality rates. Antibiotics are the only approved therapy for patients, but the widespread prevalence of antibiotic resistant strains limits treatment efficacy, and many patients succumb to the disease. Many probiotic agents are commercially available, but the mechanisms by which they benefit are not known. Understanding these mechanisms will help develop novel therapeutics that can improve healthcare, including systemic infections by S. aureus. Bacillus subtilis is a probiotic bacterium that produces an exopolysaccharide (EPS) that induces anti inflammatory macrophages (MΦ). We tested if EPS could be used for systemic S. …


White-Nose Syndrome And Immune Responses In A Resistant Bat Species (Eptesicus Fuscus), Keslie Skye Naffa Jan 2019

White-Nose Syndrome And Immune Responses In A Resistant Bat Species (Eptesicus Fuscus), Keslie Skye Naffa

MSU Graduate Theses

White-nose syndrome (WNS) has had a large negative impact on bat populations across eastern North America since its arrival in 2006. Bats affected by WNS appear to die of starvation, possibly due to the increased arousals during hibernation when there is no food present to replace the energy used to arouse. During hibernation, the bat’s immune system should be suppressed. However, once a bat of a susceptible species is exposed to the fungus that causes WNS, Psuedogymnoascus destructans (Pd), the immune system seems to respond, potentially causing an elevation in metabolic rate, which may cause the bat to …


Antibodies In The Diagnosis, Prognosis, And Prediction Of Psychotic Disorders., Thomas A Pollak, Jonathan P Rogers, Robert G Nagele, Mark Peakman, James M Stone, Anthony S David, Philip Mcguire Jan 2019

Antibodies In The Diagnosis, Prognosis, And Prediction Of Psychotic Disorders., Thomas A Pollak, Jonathan P Rogers, Robert G Nagele, Mark Peakman, James M Stone, Anthony S David, Philip Mcguire

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Blood-based biomarker discovery for psychotic disorders has yet to impact upon routine clinical practice. In physical disorders antibodies have established roles as diagnostic, prognostic and predictive (theranostic) biomarkers, particularly in disorders thought to have a substantial autoimmune or infective aetiology. Two approaches to antibody biomarker identification are distinguished: a "top-down" approach, in which antibodies to specific antigens are sought based on the known function of the antigen and its putative role in the disorder, and emerging "bottom-up" or "omics" approaches that are agnostic as to the significance of any one antigen, using high-throughput arrays to identify distinctive components of the …