Jennifer Borcherding - Academia.edu (original) (raw)

Papers by Jennifer Borcherding

A) +/tub, 192Q and 192R transgenic flies were exposed to different anoxia periods, survi... more A) +/tub, 192Q and 192R transgenic flies were exposed to different anoxia periods, survival was registered 24 hrs after reoxygenation. B) ROS level in flies measured with dihydroethdium staining. *p<0.05, ** p<0.01 when compared with +/tub.</p

+/tub and PON1 flies were exposed to anoxia for different time periods 1–4 hours. A) sur... more +/tub and PON1 flies were exposed to anoxia for different time periods 1–4 hours. A) survival registered 24 hours after reoxygenation. B) percentage of flies that recover from stupor over time. *p<0.05 when compared with +/tub.</p

Schematic representation of anoxic chamber.</p

Figure S1. Cigarette smoke extract alone does not increase bacterial growth. (A) S. aureus growth... more Figure S1. Cigarette smoke extract alone does not increase bacterial growth. (A) S. aureus growth overnight in the presence of increasing concentrations of CSE assessed by CFU. (B) P. aeruginosa overnight growth in the presence of increasing concentrations of CSE assessed by CFU. (TIFF 601Â kb)

Environmental Science: Nano, 2014

Iron Oxide Particles. The smallest iron oxide nanoparticles investigated, 2±1 nm in size, were pr... more Iron Oxide Particles. The smallest iron oxide nanoparticles investigated, 2±1 nm in size, were prepared using a synthesis method similar to that used previously for other metal oxide nanoparticles reported earlier by Wu et al 1. In the synthesis, 2.35 g (8.7 mmol) of iron chloride hexahydrate precursor was added to 40 ml methanol. The solution was the refluxed for several

Background: Paraoxonase 1 (PON1) is a protein found associated with high density lipoprotein (HDL... more Background: Paraoxonase 1 (PON1) is a protein found associated with high density lipoprotein (HDL), thought to prevent oxidative modification of low-density lipoprotein (LDL). This enzyme has been implicated in lowering the risk of cardiovascular disease. Anoxia-reoxygenation and oxidative stress are important elements in cardiovascular and cerebrovascular disease. However, the role of PON1 in anoxia-reoxygenation or anoxic injury is unclear. We hypothesize that PON1 prevents anoxia-reoxygenation injury. We set out to determine whether PON1 expression in Drosophila melanogaster protects against anoxia-reoxygenation (A-R) induced injury. Methods: Wild type (WT) and transgenic PON1 flies were exposed to anoxia (100 % Nitrogen) for different time intervals (from 1 to 24 hours). After the anoxic period, flies were placed in room air for reoxygenation. Activity and survival of flies was then recorded. Results: Within 5 minutes of anoxia, all flies fell into a stupor state. After reoxygen...

Respiratory research, Mar 10, 2018

Smoking is a leading cause of respiratory infections worldwide. Tobacco particulate matter disrup... more Smoking is a leading cause of respiratory infections worldwide. Tobacco particulate matter disrupts iron homeostasis in the lungs and increases the iron content in the airways of smokers. The airway epithelia secrete lactoferrin to quench iron required for bacteria to proliferate and cause lung infections. We hypothesized that smokers would have increased bacterial growth and biofilm formation via iron lactoferrin imbalance. We collected bronchoalveolar lavage (BAL) samples from non-smokers and smokers. We challenged these samples using a standard inoculum of Staphylococcus aureus and Pseudomonas aeruginosa and quantified bacterial growth and biofilm formation. We measured both iron and lactoferrin in the samples. We investigated the effect of supplementing non-smoker BAL with cigarette smoke extract (CSE) or ferric chloride and the effect of supplementing smoker BAL with lactoferrin on bacterial growth and biofilm formation. BAL from smokers had increased bacterial growth and biofi...

Environmental Health Perspectives

BACKGROUND: Sustained exposure to ambient particulate matter (PM) is a global cause of mortality.... more BACKGROUND: Sustained exposure to ambient particulate matter (PM) is a global cause of mortality. Coal fly ash (CFA) is a byproduct of coal combustion and is a source of anthropogenic PM with worldwide health relevance. The airway epithelia are lined with fluid called airway surface liquid (ASL), which contains antimicrobial proteins and peptides (AMPs). Cationic AMPs bind negatively charged bacteria to exert their antimicrobial activity. PM arriving in the airways could potentially interact with AMPs in the ASL to affect their antimicrobial activity. OBJECTIVES: We hypothesized that PM can interact with ASL AMPs to impair their antimicrobial activity. METHODS: We exposed pig and human airway explants, pig and human ASL, and the human cationic AMPs b-defensin-3, LL-37, and lysozyme to CFA or control. Thereafter, we assessed the antimicrobial activity of exposed airway samples using both bioluminescence and standard colonyforming unit assays. We investigated PM-AMP electrostatic interaction by attenuated total reflection Fourier-transform infrared spectroscopy and measuring the zeta potential. We also studied the adsorption of AMPs on PM. RESULTS: We found increased bacterial survival in CFA-exposed airway explants, ASL, and AMPs. In addition, we report that PM with a negative surface charge can adsorb cationic AMPs and form negative particle-protein complexes. CONCLUSION: We propose that when CFA arrives at the airway, it rapidly adsorbs AMPs and creates negative complexes, thereby decreasing the functional amount of AMPs capable of killing pathogens. These results provide a novel translational insight into an early mechanism for how ambient PM increases the susceptibility of the airways to bacterial infection.

American Journal of Respiratory Cell and Molecular Biology, 2016

Protein kinase Cζ (PKCζ) is highly expressed in the lung, where it plays several regulating roles... more Protein kinase Cζ (PKCζ) is highly expressed in the lung, where it plays several regulating roles in the pathogenesis of acute lung injury (ALI). Proliferation and differentiation of integrin β4(+) distal lung epithelial progenitor cells seem to play a key role in proper lung regeneration. We investigated the effects of a myristoylated PKCζ inhibitor (PKCζi) in a murine model of bleomycin-induced ALI. After intratracheal injury, we treated mice three times a week with PKCζi or its vehicle, DMSO. We found that mice injured with bleomycin and then treated with PKCζi for one week showed decreased activation of PKCζ, improved lung compliance, and decreased lung protein permeability compared to injured mice treated with DMSO. Mice treated continuously with PKCζi for 6 weeks showed reduced evidence of lung fibrosis by computed tomographic images, decreased lung collagen deposition, and decreased active transforming growth factor-β in the bronchoalveolar lavage fluid. In addition, we found an increased number of lung β4(+) cells compared to DMSO at Week 6. Therefore, we grew isolated integrin β4(+) lung progenitor cells in the presence of PKCζi or DMSO and found that β4(+) cells treated with PKCζi proliferated more in vitro compared to DMSO. We conclude that the use of a PKCζi promotes resolution of lung fibrosis in a bleomycin ALI model and increases the number of β4(+) progenitor cells with regenerative potential in the lung.

American Journal of Respiratory Cell and Molecular Biology, Mar 22, 2013

Recently, we reported that diesel exhaust particles (DEPs) disrupt tight junctions (TJs) in alveo... more Recently, we reported that diesel exhaust particles (DEPs) disrupt tight junctions (TJs) in alveolar epithelial cells (AECs) via an increase in reactive oxygen species (ROS). In this study, we investigated the role of protein kinase C (PKC)-ζ activation in DEP-induced lung injury. C57/bl6 mice were instilled intratracheally with 50 μl of saline containing 100 μg of DEPs or titanium dioxide (TiO2). Twenty-four hours later, bronchoalveolar lavage was performed to assess neutrophil counts and protein concentrations. In addition, in vitro experiments were performed in primary rat and human AECs exposed to DEPs (50 μg/cm(2)) for 3 hours. Transepithelial electrical conductance was measured, and TJ protein association was analyzed by immunoprecipitation. To determine whether the overexpression of antioxidants prevented DEP-induced lung injury, AECs and mice were infected with adenoviruses containing catalase and manganese superoxide dismutase (MnSOD) plasmids. In vivo, the overexpression of catalase and MnSOD prevented DEP-induced neutrophil recruitment. The inhibition of PKC-ζ activation also prevented DEP-induced neutrophil recruitment in vivo. In vitro, DEPs activated PKC-ζ in AECs, but not in alveolar macrophages. Using a specific myristolated PKC-ζ pseudosubstrate pepetide (PKC-ζ ps), we showed that PKC-ζ mediated the DEP-induced dissociation of occludin and zonula occludin-1 (ZO1) in rat and human AECs. In addition, the overexpression of constitutively active PKC-ζ induced the dissociation of occludin and ZO1 in AECs. DEP-induced TJ disruption occurs via PKC-ζ. TJ disruption seems to be in part responsible for DEP-induced lung injury.

Circulation, Nov 22, 2011

Environmental Health Perspectives, 2013

A36. EARLY EXPOSURES AND ENVIRONMENTAL EXPOSURES THAT INFLUENCE ALLERGY AND LUNG DISEASE, 2011

Page 1. / Thematic A36 EARLY EXPOSURES AND ENVIRONMENTAL EXPOSURES THAT INFLUENCE ALLERGY AND LUN... more Page 1. / Thematic A36 EARLY EXPOSURES AND ENVIRONMENTAL EXPOSURES THAT INFLUENCE ALLERGY AND LUNG DISEASE Poster Session / Sunday, May 15/8:15 AM-4:30 PM / Area C, Hall B (Upper Level), Colorado Convention Center ...

D79. EXERCISE, HYPOXIA AND ALTITUDE, 2012

D31. NON-PULMONARY CRITICAL CARE AND MONITORING, 2011

Page 1. / Thematic Poster Session / Wednesday, May 18/8:15 AM-4:30 PM D31 NON-PULMONARY CRITICAL ... more Page 1. / Thematic Poster Session / Wednesday, May 18/8:15 AM-4:30 PM D31 NON-PULMONARY CRITICAL CARE AND MONITORING / Area K, Hall B (Upper Level), Colorado Convention Center Transgenic Expression Of ...

PLoS ONE, 2013

Air pollution is a risk factor for respiratory infections, and one of its main components is part... more Air pollution is a risk factor for respiratory infections, and one of its main components is particulate matter (PM), which is comprised of a number of particles that contain iron, such as coal fly ash (CFA). Since free iron concentrations are extremely low in airway surface liquid (ASL), we hypothesize that CFA impairs antimicrobial peptides (AMP) function and can be a source of iron to bacteria. We tested this hypothesis in vivo by instilling mice with Pseudomonas aeruginosa (PA01) and CFA and determine the percentage of bacterial clearance. In addition, we tested bacterial clearance in cell culture by exposing primary human airway epithelial cells to PA01 and CFA and determining the AMP activity and bacterial growth in vitro. We report that CFA is a bioavailable source of iron for bacteria. We show that CFA interferes with bacterial clearance in vivo and in primary human airway epithelial cultures. Also, we demonstrate that CFA inhibits AMP activity in vitro, which we propose as a mechanism of our cell culture and in vivo results. Furthermore, PA01 uses CFA as an iron source with a direct correlation between CFA iron dissolution and bacterial growth. CFA concentrations used are very relevant to human daily exposures, thus posing a potential public health risk for susceptible subjects. Although CFA provides a source of bioavailable iron for bacteria, not all CFA particles have the same biological effects, and their propensity for iron dissolution is an important factor. CFA impairs lung innate immune mechanisms of bacterial clearance, specifically AMP activity. We expect that identifying the PM mechanisms of respiratory infections will translate into public health policies aimed at controlling, not only concentration of PM exposure, but physicochemical characteristics that will potentially cause respiratory infections in susceptible individuals and populations.

Environ. Health Perspect., 2013

Background: On March 20, 2010, the Icelandic volcano, Eyjafjallajökull, erupted for the first tim... more Background: On March 20, 2010, the Icelandic volcano, Eyjafjallajökull, erupted for the first time in 190 years. Despite many epidemiological reports showing volcanic ash effects on the respiratory system, there is limited data evaluating cellular mechanisms involved in the response to ash. Epidemiological work shows an increase in respiratory infections of subjects and populations exposed to volcanic eruptions. Methods: Volcanic ash was physicochemically characterized, demonstrating various sizes and presence of several transition metals, including iron. The effect of Eyjafjallajökull ash on primary alveolar and airway epithelial cells (20 to 100 1g/cm 2), human alveolar macrophages (5 to 20 1g/cm 2) and on Pseudomonas aeruginosa (PAO1) growth (2 1g/10 4 bacteria) were tested. Results: Volcanic ash had minimal effect on alveolar and airway epithelial cell integrity. In alveolar macrophages, volcanic ash disrupted pathogen killing and inflammatory responses. Volcanic ash, in in vitro bacterial growth models, increased bacterial replication and decreased bacterial killing by antimicrobial peptides. Conclusions: These results provide potential biological plausibility for epidemiological data that associates exposure to air pollution with the development of respiratory infections. These data support the conclusion that volcanic ash exposure, while not seriously compromising lung cell function, may impair innate immunity responses in exposed individuals.

C58. ENVIRONMENTAL EXPOSURES: MECHANISMS, 2012