Life Sciences Commons^™

Comparative Characteristics Of Integrin Αdβ2 Binding To Native Fibrinogen And Fibrinogen Modified By Dha Oxidation During Inflammation, Ajibola Ilesanmi

Electronic Theses and Dissertations

2-ω-carboxyethylpyrrole (CEP) is a product of docosahexaenoic acid (DHA) oxidation, which forms covalent adducts with different proteins. CEP-modified proteins can interact with macrophage receptor, integrin αDβ2. This study aims to compare αDβ2 binding to its physiological ligand, fibrinogen, and CEP-modified fibrinogen, which is formed during inflammation. We hypothesize that modification of fibrinogen changes its ligand-binding properties to integrin αDβ2 which can affect macrophage migration and retention. Recombinant αD I-domain and αDβ2-transfected HEK293 cells were used for the experiments. Using biolayer interferometry, we found that the affinity of αD I-domain binding to fibrinogen-CEP was higher than fibrinogen and inhibited by the …

Prevention Of Chronic Inflammation By Targeting Macrophage Integrin Adb2, Cady Forgey

Electronic Theses and Dissertations

Macrophage integrin a_Db₂ promotes macrophage retention and accumulation within inflamed tissue, a key event in development of chronic inflammation. Recently, the P5 peptide was identified as a specific inhibitor for integrin a_Db₂ interaction with 2-(ω-carboxyethyl) pyrole (CEP), a ligand at inflammatory sites. This thesis aims to identify integrin a_D I-domain amino acids involved in binding P5 peptide and likewise to CEP. We propose that non-conserved, basic amino acids of the integrin a_Db₂ I-domain are responsible for binding to P5 peptide and likewise to CEP. Eight amino acids were analyzed by …

Roles Of Endothelial Cell Heat Shock Protein A12b And Β-Glucan, A Reagent For Trained Immunity In The Regulation Of Inflammation In Sepsis, Fei Tu

Electronic Theses and Dissertations

Sepsis is dysregulated host immune response to infection causing life-threatening organ dysfunction. Endothelial cell dysfunction and uncontrolled inflammatory responses are two contributors for sepsis-induced mortality. The crosstalk between endothelial and immune cells plays a critical role in the pathophysiology of sepsis. Therefore, understanding the mechanism of interaction between endothelial and immune cells will provide novel information to develop therapeutic strategies for sepsis.

Pathogen associated moleculear patterns (PAMPs) and/or damage associated molecular patterns (DAMPs) produced during sepsis, activate endothelial cells to increase the expression of adhesion molecules, attracting immune cell infiltration into the tissues. Uncontrolled inflammatory responses during the early phase …

Protection Against Atherosclerosis By A Non-Native Pentameric Crp That Shares Its Ligand Recognition Functions With An Evolutionarily Distant Crp, Asmita Pathak

Electronic Theses and Dissertations

C-reactive protein (CRP) is an acute phase protein of the innate immune system that has been evolutionarily conserved. Human CRP is known to exist in two different pentameric conformations; native CRP and non-native CRP that possess differential ligand recognition functions. The structure of CRP evolved from arthropods to humans, in terms of subunit composition, disulfide bonds, and glycosylation pattern. Along with change in structure, the gene expression pattern of CRP also evolved from a constitutive protein in lower invertebrates to an acute phase protein in humans. The objective of this study was to determine the function of a non-native pentameric …

The Role Of Non-Neuronal Acetylcholine In Urogenital Chlamydial Infection, Jessica R. Lockhart

Electronic Theses and Dissertations

Chlamydia trachomatiscauses a bacterial sexually transmitted infection, Chlamydia, that is often chronic and casues reproductive complications in women. We hypothesized that Chlamydia infection increases local acetylcholine (ACh) production, which regulates the host’s inflammatory response to the infection. Female mice infected with C. muridarumwere sacrificed at days 3, 9, 15, and 21 post-infection, genital tract tissues harvested, and immunohistochemistry performed to enumerate ACh-producing cells. Infection increased the number of ACh-producing cells in cervical tissue at days 3,15, and 21 post-infection (pi), uterine tissue at day 3 and 9 pi, and ovarian tissue day 3, 15, and 21 pi. These …

An Investigation Into Fatigue Management: Effects Of Two Different Loading Protocols On Markers Of Inflammation And The Endocrine Response, Jake Bernards

Electronic Theses and Dissertations

The purposes of this dissertation were to 1) determine the effectiveness of the neutrophillymphocyte ratio (NLR) as an athlete monitoring tool in resistance training and 2) determine if repetition maximum or relative intensity loading scheme is superior in managing fatigue through the hormonal, inflammatory, and performances response throughout a 10-week periodized resistance training program. Results from the dissertation give merit to continued research regarding the use of NLR as a monitoring tool to help determine the degree of recovery. Furthermore, results from this dissertation lead to questioning the effectiveness of using a repetition maximum (RM) loading scheme within a periodized …

Exogenous Ubiquitin: Role In Myocardial Inflammation And Remodeling Post- Ischemia/Reperfusion Injury, Stephanie Scofield

Electronic Theses and Dissertations

Sympathetic stimulation occurs in the heart after injuries such as ischemia/reperfusion (I/R) and myocardial infarction and affects myocardial remodeling. Prolonged sympathetic stimulation can result in myocardial dysfunction through its effects on cardiac myocyte apoptosis and myocardial fibrosis. Ubiquitin (UB) is well known for its role of tagging old or damaged proteins for degradation via the UB-proteosome pathway. The role of exogenous UB however, is not fully understood. Previously, our lab showed that β-adrenergic receptor (β-AR) stimulation increased levels of extracellular UB in the conditioned media of adult rat ventricular myocytes and that UB inhibits β-AR-stimulated apoptosis. This study investigates the …

Cell Free Dna As A Marker Of Training Status In Weightlifters, Jeremy A. Gentles, William G. Hornsby, Christine L. Coniglio, Andy R. Dotterweich, Jon A. Miller, Charles A. Stuart, Michael H. Stone

ETSU Faculty Works

The purpose of this investigation was to elucidate the changes in cf-DNA as it relates to fluctuations in resistance training workloads and intensities. The relationship between cell free DNA (cf-DNA), C-reactive protein (CRP), creatine kinase (CK), testosterone (T), cortisol (C), testosterone-cortisol ratio (T:C), body mass and body composition were also examined. Eight weightlifters (5 males and 3 females, age = 25 ± 3.5 yr, body mass = 88.3 ± 22.7 kg, height = 173.8 ±8.4 cm) volunteered to participate in this study. Venous blood samples, body mass and body composition were taken six times, each corresponding to the end of …

Mechanism Of Transcriptional Regulation Of C-Reactive Protein Gene Expression., Bhavya Voleti

Electronic Theses and Dissertations

C-reactive protein (CRP) is an acute phase protein produced by hepatocytes whose serum concentration increases in inflammatory conditions including cardiovascular complications. Statins that are used in the treatment of cardiovascular diseases to reduce cholesterol also lower serum CRP levels. In human hepatoma Hep3B cells, CRP is induced in response to cytokines IL-6 and IL-1β. The objective of the study was to determine the mechanism of regulation of CRP gene expression in Hep3B cells in response to cytokines and to determine the effect of statins on CRP expression. Key findings of our research were: 1. IL-1β-activated NF-κB p50/p65 acted synergistically with …