Medicine and Health Sciences Commons^™

Hsp70 Is A Critical Regulator Of Hsp90 Inhibitor's Effectiveness In Preventing Hcl-Induced Chronic Lung Injury And Pulmonary Fibrosis, Ruben M. L. Colunga Biancatelli, Pavel A. Solopov, Tierney Day, Betsy Gregory, Michael Osei-Nkansah, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

Exposure to hydrochloric acid (HCl) can provoke acute and chronic lung injury. Because of its extensive production for industrial use, frequent accidental exposures occur, making HCl one of the top five chemicals causing inhalation injuries. There are no Food and Drug Administration (FDA)-approved treatments for HCl exposure. Heat shock protein 90 (HSP90) inhibitors modulate transforming growth factor-β (TGF-β) signaling and the development of chemical-induced pulmonary fibrosis. However, little is known on the role of Heat Shock Protein 70 (HSP70) during injury and treatment with HSP90 inhibitors. We hypothesized that administration of geranylgeranyl-acetone (GGA), an HSP70 inducer, or gefitinib (GFT), an …

Cancer Cell-Specific Cgas/Sting Signaling Pathway In The Era Of Advancing Cancer Cell Biology, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Graduate Studies Faculty Publications

Pattern-recognition receptors (PRRs) are critical to recognizing endogenous and exogenous threats to mount a protective proinflammatory innate immune response. PRRs may be located on the outer cell membrane, cytosol, and nucleus. The cGAS/STING signaling pathway is a cytosolic PRR system. Notably, cGAS is also present in the nucleus. The cGAS-mediated recognition of cytosolic dsDNA and its cleavage into cGAMP activates STING. Furthermore, STING activation through its downstream signaling triggers different interferon-stimulating genes (ISGs), initiating the release of type 1 interferons (IFNs) and NF-κB-mediated release of proinflammatory cytokines and molecules. Activating cGAS/STING generates type 1 IFN, which may prevent cellular transformation …

Maackia Amurensis Seed Lectin (Masl) Increases Movement Velocity Of Mice With Tnfα Induced Rheumatoid Arthritis, Amanda A. Greenspan, Kelly L. Hamilton, Alan J. Shienbaum, Bradford Fischer, Andrea Bottaro, Gary S. Goldberg

Rowan-Virtua Research Day

Up to 70 million people around the world suffer from rheumatoid arthritis. Current treatment options have varied efficacy and can cause unwanted side effects. New approaches are needed to treat this condition. Sialic acid modifications on chondrocyte receptors have been associated with arthritic inflammation and joint destruction. The transmembrane mucin receptor protein podoplanin (PDPN) has been identified as a functionally relevant receptor that presents extracellular sialic acid motifs. PDPN signaling promotes inflammation and invasion associated with arthritis and, therefore, has emerged as a target that can be used to inhibit arthritic inflammation. Maackia amurensis seed lectin (MASL) can target PDPN …

The Role Of The Nlrp3 Inflammasome In Alzheimer's Disease, Ethan S. Terman

Undergraduate Research Posters

This study examines the consequences of Alzheimer’s in rat and mice test subjects. The goal is to identify the effects of certain NLRP3 inhibiting drugs and to see if there are any noticeable effects in regards to impeding the pathological development of Alzheimer’s disease. The results are visualized by implementing the immunohistochemical process to identify neurodegeneration in the brain and to assess the expression levels of amyloid beta as an indicator of Alzheimer’s pathology. Other tests are also conducted on these transgenic mice to gauge cognitive functioning levels during the onset of their disease, those being behavior tests, but not …

Deconstructing Sex Differences In C-Reactive Protein Trends Over Time, Ashley W. Kranjac, Dinko Kranjac, Olivia Lounsbury

Sociology Faculty Articles and Research

Objectives

Heightened inflammatory state, as measured by circulating C-reactive protein (CRP) levels, can promote inflammation-mediated disease risk. It is important to account for population fluctuation and sex variation in serum CRP concentrations on overall time trends.

Methods

Using the National Health and Nutrition Examination Survey data, we specify linear and algebraic decomposition models separately by sex to identify the drivers of the changing trends in the distribution of CRP values in the population.

Results

We found a nonsignificant overall increase in CRP, but a significant decrease among women and increase among men, over a 10-year period. We then used linear …

Recombinant Human Proteoglycan-4 Mediates Interleukin-6 Response In Both Human And Mouse Endothelial Cells Induced Into A Sepsis Phenotype, Holly A. Richendrfer, Mitchell M. Levy, Khaled A. Elsaid, Tannin A. Schmidt, Ling Zhang, Ralph Cabezas, Gregory D. Jay

Pharmacy Faculty Articles and Research

Objectives:

Sepsis is a leading cause of death in the United States. Putative targets to prevent systemic inflammatory response syndrome include antagonism of toll-like receptors 2 and 4 and CD44 receptors in vascular endothelial cells. Proteoglycan-4 is a mucinous glycoprotein that interacts with CD44 and toll-like receptor 4 resulting in a blockade of the NOD-like receptor pyrin domain-containing-3 pathway. We hypothesized that endothelial cells induced into a sepsis phenotype would have less interleukin-6 expression after recombinant human proteoglycan 4 treatment in vitro.

Design:

Enzyme-linked immunosorbent assay and reverse transcriptase-quantitative polymerase chain reaction to measure interleukin-6 protein and gene expression.

Setting: …

Serum Amyloid A3 Is A High Density Lipoprotein-Associated Acute-Phase Protein, Lisa R. Tannock, Maria C. De Beer, Ailing Ji, Preetha Shridas, Victoria P. Noffsinger, Laura Den Hartigh, Alan Chait, Frederick C. De Beer, Nancy R. Webb

Internal Medicine Faculty Publications

Serum amyloid A (SAA) is a family of acute-phase reactants. Plasma levels of human SAA1/SAA2 (mouse SAA1.1/2.1) can increase ≥ 1,000-fold during an acute-phase response. Mice, but not humans, express a third relatively understudied SAA isoform, SAA3. We investigated whether mouse SAA3 is an HDL-associated acute-phase SAA. Quantitative RT-PCR with isoform-specific primers indicated that SAA3 and SAA1.1/2.1 are induced similarly in livers (∼2,500-fold vs. ∼6,000-fold, respectively) and fat (∼400-fold vs. ∼100-fold, respectively) of lipopolysaccharide (LPS)-injected mice. In situ hybridization demonstrated that all three SAAs are produced by hepatocytes. All three SAA isoforms were detected in plasma of LPS-injected mice, although …

Myeloperoxidase-Mediated Protein Lysine Oxidation Generates 2- Aminoadipic Acid And Lysine Nitrile In Vivo, Hongqiao Lin, Bruce S. Levison, Jennifer A. Buffa, Ying Huang, Xiaoming Fu, Zeneng Wang, Valentin Gogonea, Joseph A. Didonato, Stanley L. Hazen

Chemistry Faculty Publications

Recent studies reveal 2-aminoadipic acid (2-AAA) is both elevated in subjects at risk for diabetes and mechanistically linked to glucose homeostasis. Prior studies also suggest enrichment of protein-bound 2-AAA as an oxidative post-translational modification of lysyl residues in tissues associated with degenerative diseases of aging. While in vitro studies suggest redox active transition metals or myeloperoxidase (MPO) generated hypochlorous acid (HOCl) may produce protein-bound 2-AAA, the mechanism(s) responsible for generation of 2- AAA during inflammatory diseases are unknown. In initial studies we observed that traditional acid- or basecatalyzed protein hydrolysis methods previously employed to measure tissue 2-AAA can artificially generate …

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 …

Stimulation Through Tlr4 Increases Fviii Inhibitor Formation In A Mouse Model Of Hemophilia A, Claire K. Holley

Dissertations & Theses (Open Access)

Hemophilia A is a clotting disorder caused by functional factor VIII (FVIII) deficiency. About 25% of patients treated with therapeutic recombinant FVIII develop antibodies (inhibitors) that render subsequent FVIII treatments ineffective. The immune mechanisms of inhibitor formation are not entirely understood, but circumstantial evidence indicates a role for increased inflammatory response, possibly via stimulation of Toll-like receptors (TLRs), at the time of FVIII immunization. I hypothesized that stimulation through TLR4 in conjunction with FVIII treatments would increase the formation of FVIII inhibitors. To test this hypothesis, FVIII K.O. mice were injected with recombinant human FVIII with or without concomitant doses …