Environmental Public Health Commons^™

Blocking Interleukin 33 Reduces Joint, Systemic, And Lung Inflammatory Responses In The Combined Collagen-Induced Arthritis-Inhalant Endotoxin Exposure Model, Jill A. Poole, Jacob L. Larsen, Geoffrey M. Thiele, Todd A. Wyatt, Amy J. Nelson, Michael J. Duryee, Angela Gleason, Oliver W. Schanze, Aaron D. Schwab, John D. Dickinson, Deanna Mosley, Michael Lush, Han-Jun Wang, E. Suzanne Cohen, Bryant England, Ted R. Mikuls

Journal Articles: Environmental, Agricultural & Occupational Health

Therapies capable of resolving rheumatoid arthritis (RA)-associated lung disease, particularly in the setting of environmental exposures, are lacking. This study sought to determine whether blocking interleukin (IL)-33 in a murine model of RA-associated lung disease induced by combined collagen-induced arthritis (CIA) and repeated inhalant lipopolysaccharide (LPS) exposures could be advantageous. Arthritis prone male DBA/1J mice received CIA (vs saline) injections (days 1 and 21) plus intranasal LPS (100 ng) or saline daily for 4 weeks and were subsequently treated with 5 doses of anti-IL-33 (10 mg/kg) or isotype over 11 days. Anti-IL-33 therapy significantly (P < .05) mitigated several CIA+LPS-induced effects. Anti-IL-33 reduced arthritis inflammatory score by 76% and serum acute phase reactant pentraxin-2 by 70% and reversed weight loss induced by CIA+LPS coexposure. Anti-IL-33 reduced CIA+LPS-induced antimalondialdehyde acetaldehyde but not anticitrullinated autoantibodies in serum and reduced serum levels of inflammatory mediators. Lung cell infiltrates induced by coexposure, including neutrophils, activated lung macrophages, transitional monocytes-macrophages, monocytic-like cells, and dendritic cells, were reduced with anti-IL-33. Anti-IL-33 also reduced CIA+LPS-induced lung levels of chemokines involved in monocyte-macrophage recruitment and fibrotic/repair mediators collagen deposition, IL-33 expression, inflammatory CC motif chemokine receptor 2

A Zinc Chelate Of Lysine/Glutamic Acid Reduces Alcohol-Induced Ciliary Dysfunction, Emily Do, Daren L. Knoell, Christopher Bauer, Deanna Mosley, Deandra R. Smith, Derrick R. Samuelson, Todd A. Wyatt

Journal Articles: Environmental, Agricultural & Occupational Health

Alcohol misuse is a known risk factor for pneumonia, and up to 50% of individuals who misuse alcohol are zinc deficient. Chronic alcohol misuse can lead to alcohol-induced ciliary dysfunction (AICD), preventing effective mucociliary clearance and protection against lung infection. Because zinc salts fail to alter AICD, we hypothesized a form of zinc (Zinpro Zinc LG) with enhanced cell uptake would protect against AICD. Human and mouse airway epithelial cells were treated with 50 mM ethanol for 1-24 h followed by the ciliostimulatory agents. Cilia beat frequency (CBF) and cAMP-dependent protein kinase (PKA) activity were assayed. Cyclic AMP or beta …

Lung-Delivered Il-10 Mitigates Lung Inflammation Induced By Repeated Endotoxin Exposures In Male Mice, Aaron Schwab, Todd A. Wyatt, Oliver Schanze, Amy J. Nelson, Angela Gleason, Michael J. Duryee, Deanna Mosley, Geoffrey M. Thiele, Ted R. Mikuls, Jill A. Poole

Journal Articles: Environmental, Agricultural & Occupational Health

Therapies capable of resolving inflammatory lung disease resulting from high-consequence occupational/environmental hazards are lacking. This study seeks to determine the therapeutic potential of direct lung-delivered interleukin (IL)-10 following repeated lipopolysaccharide exposures. C57BL/6 mice were intratracheally instilled with LPS (10 μg) and treated with IL-10 (1 μg) or vehicle control for 3 days. Lung cell infiltrates were enumerated by flow cytometry. Lung sections were stained for myeloperoxidase (MPO), CCR2, vimentin, and post-translational protein citrullination (CIT) and malondialdehyde-acetaldehyde (MAA) modifications. Lung function testing and longitudinal in vivo micro-CT imaging were performed. Whole lungs were profiled using bulk RNA sequencing. IL-10 treatment reduced …

Lung Disease In Relation To Unique Monocyte-Macrophage Subpopulations Induced By Combined Inhalant Endotoxin And Collagen-Induced Arthritis, Jill A. Poole, Aaron Schwab, Geoffrey M. Thiele, Todd A. Wyatt, Amy J. Nelson, Oliver Schanze, Angela Gleason, Michael J. Duryee, Bryant England, Ted R. Mikuls

Journal Articles: Environmental, Agricultural & Occupational Health

BACKGROUND: Lung disease is the most overrepresented cause of death in rheumatoid arthritis (RA). Animal studies have demonstrated potentiated autoimmunity, arthritis, and profibrotic/inflammatory lung disease with a combination of airborne exposures and collagen-induced arthritis (CIA), a model that recapitulates features of RA-associated interstitial lung disease (RA-ILD). As patients with RA-ILD demonstrate unique circulating monocyte subpopulations, this study aims to characterize lung infiltrating monocytes/macrophages in a mouse model of RA-ILD and determine whether reducing these cells mitigates the development of lung disease.

METHODS: Autoimmune-prone DBA/1J mice received intranasal inhalation of lipopolysaccharide (LPS) daily for up to 5 weeks and CIA induction. …

Targeted Deletion Of Cxcl1 In Mscs Regulates Osteogenesis And Suppresses Bone-Metastatic Prostate Cancer, Catherine S. Johnson, Diane L. Costanzo-Garvey, Julio C. Valencia, Sanjana Rajgopal, Theodore Reed, Emma R. Brannon, Jeremy S. Frieling, Deanna Mosley, Todd A. Wyatt, Elijah F. Edmondson, Kabhilan Mohan, Grinu Mathew, Leah M. Cook

Journal Articles: Environmental, Agricultural & Occupational Health

Bone metastasis continues to be the greatest challenge in treating patients with prostate cancer despite ongoing research. In bone, prostate cancer tumors hijack normal bone remodeling processes to drive cancer progression. However, it is unclear how these interactions drive bone-metastatic prostate cancer growth in the bone environment. To understand the mechanisms associated with bone-metastatic prostate cancer regulation of mesenchymal stem cells (MSC), we previously identified that bone-metastatic prostate cancer induces MSC expression of the pro-inflammatory chemokine CXCL8 and its mouse functional homologue Cxcl1. To date, there has been little to no information about the role of CXCL1/8 in MSC biology …

The Alcohol Exposome, Nousha H. Sabet, Todd A. Wyatt

Journal Articles: Environmental, Agricultural & Occupational Health

Science is now in a new era of exposome research that strives to build a more all-inclusive, panoramic view in the quest for answers; this is especially true in the field of toxicology. Alcohol exposure researchers have been examining the multivariate co-exposures that may either exacerbate or initiate alcohol-related tissue/organ injuries. This manuscript presents selected key variables that represent the Alcohol Exposome. The primary variables that make up the Alcohol Exposome can include comorbidities such as cigarettes, poor diet, occupational hazards, environmental hazards, infectious agents, and aging. In addition to representing multiple factors, the Alcohol Exposome examines the various types …

Organic Dust Exposure Enhances Sars-Cov-2 Entry In A Pkcα- And Adam-17-Dependent Manner, Abenaya Muralidharan, Christopher Bauer, Claire Nissen, St. Patrick Reid, Jill A. Poole, Todd A. Wyatt

Journal Articles: Environmental, Agricultural & Occupational Health

No abstract provided.

Health Vulnerability Mapping For Drought: A Case Study In A Predominantly Rural, Agricultural State, Babak Jalalzadeh-Fard, Jagadeesh Puvvula, Kelly Smith, Michael Hayes, Rachel Lookadoo, Rezaul Mahmood, Sharon J. Medcalf, Clinton Rowe, Martha Durr, Jesse E. Bell

Journal Articles: Environmental, Agricultural & Occupational Health

No abstract provided.

Synergistic Detrimental Effects Of Cigarette Smoke, Alcohol, And Sars-Cov-2 In Copd Bronchial Epithelial Cells, Abenaya Muralidharan, Christopher Bauer, Dawn M. Katafiasz, Heather M. Strah, Aleem Siddique, St. Patrick Reid, Kristina L. Bailey, Todd A. Wyatt

Journal Articles: Environmental, Agricultural & Occupational Health

Lung conditions such as COPD, as well as risk factors such as alcohol misuse and cigarette smoking, can exacerbate COVID-19 disease severity. Synergistically, these risk factors can have a significant impact on immunity against pathogens. Here, we studied the effect of a short exposure to alcohol and/or cigarette smoke extract (CSE) in vitro on acute SARS-CoV-2 infection of ciliated human bronchial epithelial cells (HBECs) collected from healthy and COPD donors. We observed an increase in viral titer in CSE- or alcohol-treated COPD HBECs compared to untreated COPD HBECs. Furthermore, we treated healthy HBECs accompanied by enhanced lactate dehydrogenase activity, indicating …

Self-Reported Respiratory Health Symptoms And Respiratory Protection Behaviors Of Young Adult Hog Producers In The United States, Jenna L. Gibbs, Carolyn Sheridan, David Sullivan, Risto Rautiainen, Matthew W. Nonnenmann, Todd A. Wyatt

Journal Articles: Environmental, Agricultural & Occupational Health

INTRODUCTION AND METHODS: In this study, we evaluated self-reported respiratory symptoms during agricultural work, respiratory protection use and experience, and perceived value of receiving respirators using Gear Up for Ag Health and Safety Program™ pre- and post-surveys from 703 to 212 young adult hog producers in the United States. To our knowledge, this is one of the most extensive survey data sets on self-reported respiratory symptoms and respiratory protection behaviors of collegiate-aged young adults working in US livestock production.

RESULTS: About one-third (37%) of young adult hog producers stated that they have experienced cough, shortness of breath, fever, and chills …

Human Alcohol-Microbiota Mice Have Increased Susceptibility To Bacterial Pneumonia, Kelly C. Cunningham, Deandra R. Smith, Daniel Villageliu, Christi M. Ellis, Amanda E. Ramer-Tait, Jeffrey D. Price, Todd A. Wyatt, Daren L. Knoell, Mystera M. Samuelson, Patricia E Molina, David A. Welsh, Derrick R. Samuelson

Journal Articles: Environmental, Agricultural & Occupational Health

Preclinical studies have shown that chronic alcohol abuse leads to alterations in the gastrointestinal microbiota that are associated with behavior changes, physiological alterations, and immunological effects. However, such studies have been limited in their ability to evaluate the direct effects of alcohol-associated dysbiosis. To address this, we developed a humanized alcohol-microbiota mouse model to systematically evaluate the immunological effects of chronic alcohol abuse mediated by intestinal dysbiosis. Germ-free mice were colonized with human fecal microbiota from individuals with high and low Alcohol Use Disorders Identification Test (AUDIT) scores and bred to produce human alcohol-associated microbiota or human control-microbiota F1 progenies. …

Zip8-Mediated Intestinal Dysbiosis Impairs Pulmonary Host Defense Against Bacterial Pneumonia, Derrick R. Samuelson, Deandra R. Smith, Kelly C. Cunningham, Todd A. Wyatt, Sannette C. Hall, Daryl J. Murry, Yashpal S. Chhonker, Daren L. Knoell

Journal Articles: Environmental, Agricultural & Occupational Health

Pneumococcal pneumonia is a leading cause of morbidity and mortality worldwide. An increased susceptibility is due, in part, to compromised immune function. Zinc is required for proper immune function, and an insufficient dietary intake increases the risk of pneumonia. Our group was the first to reveal that the Zn transporter, ZIP8, is required for host defense. Furthermore, the gut microbiota that is essential for lung immunity is adversely impacted by a commonly occurring defective ZIP8 allele in humans. Taken together, we hypothesized that loss of the ZIP8 function would lead to intestinal dysbiosis and impaired host defense against pneumonia. To …

Sars-Cov-2 Dysregulates Neutrophil Degranulation And Reduces Lymphocyte Counts, Abenaya Muralidharan, Todd A. Wyatt, St. Patrick Reid

Journal Articles: Environmental, Agricultural & Occupational Health

SARS-CoV-2, the virus that causes COVID-19, has given rise to one of the largest pandemics, affecting millions worldwide. High neutrophil-to-lymphocyte ratios have been identified as an important correlate to poor recovery rates in severe COVID-19 patients. However, the mechanisms underlying this clinical outcome and the reasons for its correlation to poor prognosis are unclear. Furthermore, the mechanisms involved in healthy neutrophils acquiring a SARS-CoV-2-mediated detrimental role are yet to be fully understood. In this study, we isolated circulating neutrophils from healthy donors for treatment with supernates from infected epithelial cells and direct infection with SARS-CoV-2 in vitro. Infected epithelial cells …

Aldehyde Trapping By Adx-102 Is Protective Against Cigarette Smoke And Alcohol Mediated Lung Cell Injury, Carmen A. Ochoa, Claire Nissen, Deanna Mosley, Christopher Bauer, Destiny Jordan, Kristina L. Bailey, Todd A. Wyatt

Journal Articles: Environmental, Agricultural & Occupational Health

Most individuals diagnosed with alcohol use disorders smoke cigarettes. Large concentrations of malondialdehyde and acetaldehyde are found in lungs co-exposed to cigarette smoke and alcohol. Aldehydes directly injure lungs and form aldehyde protein adducts, impacting epithelial functions. Recently, 2-(3-Amino-6-chloroquinolin-2-yl)propan-2-ol (ADX-102) was developed as an aldehyde-trapping drug. We hypothesized that aldehyde-trapping compounds are protective against lung injury derived from cigarette smoke and alcohol co-exposure. To test this hypothesis, we pretreated mouse ciliated tracheal epithelial cells with 0–100 µM of ADX-102 followed by co-exposure to 5% cigarette smoke extract and 50 mM of ethanol. Pretreatment with ADX-102 dose-dependently protected against smoke and …

Surface Modification Of Biodegradable Microparticles With The Novel Host-Derived Immunostimulant Cpdi-02 Significantly Increases Short-Term And Long-Term Mucosal And Systemic Antibodies Against Encapsulated Protein Antigen In Young Naïve Mice After Respiratory Immunization, Jacob E. Parriott, Jason P. Stewart, D. David Smith, Stephen M. Curran, Christopher D. Bauer, Todd A. Wyatt, Joy A. Phillips, Elizabeth Lyden, Geoffrey M. Thiele, Joseph A. Vetro Phd

Journal Articles: Environmental, Agricultural & Occupational Health

Generating long-lived mucosal and systemic antibodies through respiratory immunization with protective antigens encapsulated in nanoscale biodegradable particles could potentially decrease or eliminate the incidence of many infectious diseases, but requires the incorporation of a suitable mucosal immunostimulant. We previously found that respiratory immunization with a model protein antigen (LPS-free OVA) encapsulated in PLGA 50:50 nanoparticles (~380 nm diameter) surface-modified with complement peptide-derived immunostimulant 02 (CPDI-02; formerly EP67) through 2 kDa PEG linkers increases mucosal and systemic OVA-specific memory T-cells with long-lived surface phenotypes in young, naïve female C57BL/6 mice. Here, we determined if respiratory immunization with LPS-free OVA encapsulated in …

Post-Endotoxin Exposure-Induced Lung Inflammation And Resolution Consequences Beneficially Impacted By Lung-Delivered Il-10 Therapy, Jill A. Poole, Rohit Gaurav, Aaron Schwab, Amy J. Nelson, Angela Gleason, Debra J. Romberger, Todd A. Wyatt

Journal Articles: Environmental, Agricultural & Occupational Health

Although lung diseases typically result from long-term exposures, even a robust, one-time exposure can result in long-lasting consequences. Endotoxin is a ubiquitous environmental/occupational inflammatory agent often used to model airway inflammation. Using a murine model, the return to lung homeostasis following high dose inhalant lipopolysaccharide (LPS, 10-100 μg) exposure were delineated over 2 weeks. LPS-induced rapid weight loss, release of proinflammatory mediators, and inflammatory cell influx with prolonged persistence of activated macrophages CD11c⁺CD11b⁺ and recruited/transitioning CD11c^intCD11b⁺ monocyte-macrophages out to 2 weeks. Next, lung-delivered recombinant (r) interleukin (IL)-10 was intratracheally administered for 3 doses initiated …

Covid-19 Patients With Documented Alcohol Use Disorder Or Alcohol-Related Complications Are More Likely To Be Hospitalized And Have Higher All-Cause Mortality, Kristina L. Bailey, Harlan Sayles, James Campbell, Neha Khalid, Madyson Anglim, Jana Ponce, Todd A. Wyatt, James C. Mcclay, Ellen L. Burnham, Alfred Anzalone, Corrine K. Hanson

Journal Articles: Environmental, Agricultural & Occupational Health

BACKGROUND: Coronavirus Disease 2019 (COVID-19) has affected every country globally, with hundreds of millions of people infected with the SARS-CoV-2 virus and over 6 million deaths to date. It is unknown how alcohol use disorder (AUD) affects the severity and mortality of COVID-19. AUD is known to increase the severity and mortality of bacterial pneumonia and the risk of developing acute respiratory distress syndrome. Our objective is to determine whether individuals with AUD have increased severity and mortality from COVID-19.

METHODS: We utilized a retrospective cohort study of inpatients and outpatients from 44 centers participating in the National COVID Cohort …

Neutralization Of Il-33 Modifies The Type 2 And Type 3 Inflammatory Signature Of Viral Induced Asthma Exacerbation, Kristi J. Warren, Jill A. Poole, Jenea M. Sweeter, Jane M. Devasure, John D. Dickinson, R. Stokes Peebles, Todd A. Wyatt

Journal Articles: Environmental, Agricultural & Occupational Health

BACKGROUND: Respiratory viral infections are one of the leading causes of need for emergency care and hospitalizations in asthmatic individuals, and airway-secreted cytokines are released within hours of viral infection to initiate these exacerbations. IL-33, specifically, contributes to these allergic exacerbations by amplifying type 2 inflammation. We hypothesized that blocking IL-33 in RSV-induced exacerbation would significantly reduce allergic inflammation.

METHODS: Sensitized BALB/c mice were challenged with aerosolized ovalbumin (OVA) to establish allergic inflammation, followed by RSV-A2 infection to yield four treatment groups: saline only (Saline), RSV-infected alone (RSV), OVA alone (OVA), and OVA-treated with RSV infection (OVA-RSV). Lung outcomes included …

Nuclear Factor Kappa-B Contributes To Cigarette Smoke Tolerance In Pancreatic Ductal Adenocarcinoma Through Cysteine Metabolism, Venugopal Gunda, Yashpal S Chhonker, Nagabhishek Sirpu Natesh, Pratima Raut, Sakthivel Muniyan, Todd A. Wyatt, Daryl J. Murry, Surinder K. Batra, Satyanarayana Rachagani

Journal Articles: Environmental, Agricultural & Occupational Health

BACKGROUND: Retrospective studies revealed that cigarette smoking enhances risk of incidence and worsens prognosis in pancreatic cancer (PC) patients. Poor prognosis in smoker cohort of PC patients indicates prevalence of cigarette smoke stimulated survival mechanisms yet to be explored in PC. In this study, cigarette smoke induced metabolic pathways were explored and targeted in PC.

METHODS: Human pancreatic ductal adenocarcinoma cell (PDAC) lines, genetically engineered mice models (GEMMs), mass spectrometry based heavy isotope-based metabolite analysis, cytotoxicity assays and Nuclear factor kappa-B (NF-kB) targeting were utilized in this study. Cigarette smoke extract (CSE) was prepared fresh each day by bubbling cell …

Dual Substance Use Of Electronic Cigarettes And Alcohol, Tanner J. Wetzel, Todd A. Wyatt

Journal Articles: Environmental, Agricultural & Occupational Health

Electronic cigarettes (ECs) are a modern nicotine delivery system that rapidly grew in widespread use, particularly in younger populations. Given the long history of the comorbidity of alcohol and nicotine use, the rising prevalence of ECs raises the question as to their role in the consumption of alcohol. Of the numerous models of ECs available, JUUL is the most popular. This narrative review aims to determine current trends in literature regarding the relationship between EC and alcohol dual use, as well as hypothesize potential pathogenic tissue damage and summarize areas for future study, including second-hand vapor exposure and calling for …

Ovalbumin-Sensitized Mice Have Altered Airway Inflammation To Agriculture Organic Dust, Kristi J. Warren, John D. Dickinson, Amy J. Nelson, Todd A. Wyatt, Debra J. Romberger, Jill A. Poole

Journal Articles: Environmental, Agricultural & Occupational Health

Agriculture exposures are associated with reducing the risk of allergy and asthma in early life; yet, repeated exposures later in life are associated with chronic bronchitis and obstructive pulmonary diseases. The objective of this study was to investigate the airway inflammatory response to organic dust extract (ODE) in mice with established ovalbumin (OVA)-induced experimental asthma. C57BL/6 mice were either OVA sensitized/aerosol-exposed or saline (Sal) sensitized/aerosol-challenged. Both groups were then subsequently challenged once with intranasal saline or swine confinement ODE to obtain 4 treatment groups of Sal-Sal, Sal-ODE, OVA-Sal, and OVA-ODE. Airway hyper-responsiveness (AHR) to methacholine, bronchiolar lavage fluid, lung tissues, …

Organic Barn Dust Inhibits Surfactant Protein D Production Through Protein Kinase-C Alpha Dependent Increase Of Gpr116, David Schneberger, Jane M. Devasure, Shelley A. Kirychuk, Todd A. Wyatt

Journal Articles: Environmental, Agricultural & Occupational Health

Prolonged exposure to organic barn dusts can lead to chronic inflammation and a broad range of lung problems over time, mediated by innate immune mechanisms. The immune surfactant or collectin surfactant protein D (SP-D) is a crucial multifunctional innate immune receptor. Little work to date has examined the effect of such collectins in response to organic dusts. We provide evidence here that agricultural organic dusts can inhibit mRNA and protein expression of SP-D in a human alveolar epithelial cell line, and an in vivo mouse model. This inhibition was not a result of lipopolysaccharide (LPS) or peptidoglycans, the two most …

Malondialdehyde-Acetaldehyde (Maa) Adducted Surfactant Protein Induced Lung Inflammation Is Mediated Through Scavenger Receptor A (Sr-A1)., Muna Sapkota, Jane M. Devasure, Kusum K. Kharbanda, Todd A. Wyatt

Journal Articles: Environmental, Agricultural & Occupational Health

BACKGROUND: Co-exposure to cigarette smoke and alcohol leads to the generation of high concentrations of acetaldehyde and malondialdehyde in the lung. These aldehydes being highly electrophilic in nature react with biologically relevant proteins such as surfactant protein D (SPD) through a Schiff base reaction to generate SPD adducted malondialdehyde-acetaldehyde adduct (SPD-MAA) in mouse lung. SPD-MAA results in an increase in lung pro-inflammatory chemokine, keratinocyte chemoattractant (KC), and the recruitment of lung lavage neutrophils. Previous in vitro studies in bronchial epithelial cells and macrophages show that scavenger receptor A (SR-A1/CD204) is a major receptor for SPD-MAA. No studies have yet examined …