A5082352781- Asthma and respiratory diseases
- Immune Cell Function and Interaction
- Chronic Obstructive Pulmonary Disease (COPD) Research
- IL-33, ST2, and ILC Pathways
- Pediatric health and respiratory diseases
- Neonatal Respiratory Health Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Immune Response and Inflammation
- Medical Practices and Rehabilitation
- Cell Adhesion Molecules Research
- Receptor Mechanisms and Signaling
- Eosinophilic Disorders and Syndromes
- Histiocytic Disorders and Treatments
- Glycosylation and Glycoproteins Research
- Tuberous Sclerosis Complex Research
- Cancer Immunotherapy and Biomarkers
- Respiratory and Cough-Related Research
- Indoor Air Quality and Microbial Exposure
- Allergic Rhinitis and Sensitization
- Eosinophilic Esophagitis
- Respiratory Support and Mechanisms
- S100 Proteins and Annexins
- Cerebral Palsy and Movement Disorders
- Bone health and osteoporosis research
- Neuropeptides and Animal Physiology
University of Cincinnati Medical Center
2013-2024
University of Cincinnati
2007-2024
Springer Nature (Germany)
2024
Cincinnati Children's Hospital Medical Center
2005-2023
Zoetis (United States)
2023
Pacific Northwest National Laboratory
2023
Cincinnati VA Medical Center
2021-2023
Pulmonary and Critical Care Associates
2008-2021
SleepMed
2021
Veterans Health Administration
2018-2020
Abstract Intracellular 1,25-dihydroxyvitamin D receptor (VDR) is expressed in human skeletal muscle tissue. However, it unknown whether VDR expression vivo related to age or vitamin status, differs between groups. Introduction: We investigated these factors and their relation freshly removed Materials Methods: biopsy specimens of the gluteus medius taken at surgery from 20 female patients undergoing total hip arthroplasty (mean age, 71.6 ± 14.5; 72% > 65 years) transversospinalis 12...
Nitrotyrosine is widely used as a marker of post-translational modification by the nitric oxide (<sup>⋅</sup>NO, nitrogen monoxide)-derived oxidant peroxynitrite (ONOO<sup>−</sup>). However, since discovery that myeloperoxidase (MPO) and eosinophil peroxidase (EPO) can generate nitrotyrosine via oxidation nitrite (NO <mml:math><mml:mrow></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow><mml:mrow><mml:mo>−</mml:mo></mml:mrow></mml:math>), several questions have arisen. First, relative...
Metformin slows tumor growth and progression in vitro, combination with chemoradiotherapy, resulted high overall survival patients head neck cancer squamous cell carcinoma (HNSCC) our phase 1 clinical trial (NCT02325401). is also postulated to activate an antitumor immune response. Here, we investigate immunologic effects of metformin on natural killer (NK) T cells, including results from two I open-label studies HNSCC treated (NCT02325401, NCT02083692).Peripheral blood was collected before...
Abstract Asthma and mouse models of allergic respiratory inflammation are invariably associated with a pulmonary eosinophilia; however, this association has remained correlative. In report, causative relationship between eosinophils allergen-provoked pathologies was established using eosinophil adoptive transfer. Eosinophils were transferred directly into the lungs either naive or OVA-treated IL-5−/− mice. This strategy resulted in eosinophilia equivalent to that observed wild-type animals....
Chronic obstructive pulmonary disease is marked by alveolar enlargement and excess production of airway mucus. Acrolein, a component cigarette smoke, increases mucin 5AC (MUC5AC), prevalent in NCI-H292 cells transcriptional activation, but the signal transduction pathways involved acrolein-induced MUC5AC expression are unknown. Acrolein depleted cellular glutathione at doses 10 muM or greater, higher than those sufficient (0.03 muM) to increase mRNA, suggesting that was independent oxidative...
Immune surveillance of the airways is critical to maintain integrity and health lung. We have identified a family ligands expressed on surface stressed airway epithelial cells whose function bind NKG2D-activating receptor found several pulmonary lymphocytes, including natural killer cells, gammadelta(+) T CD8(+) cells. employed real-time PCR flow cytometry in normal transformed cell demonstrate that major histocompatibility complex class I chain-related (MIC) B UL-16 binding protein (ULBP)...
Chronic obstructive pulmonary disease (COPD), a global public health problem, is characterized by progressive difficulty in breathing, with increased mucin production, especially the small airways. Acrolein, constituent of cigarette smoke and an endogenous mediator oxidative stress, increases airway 5, subtypes A C (MUC5AC) production; however, mechanism remains unclear. In this study, mMUC5AC transcripts protein were associated lung matrix metalloproteinase 9 (mMMP9) transcripts, protein,...
Abstract The role of adaptive immunity in the development or progression chronic obstructive pulmonary disease (COPD) remains undefined. Recently, presence autoantibodies and autoreactive T cells has been demonstrated COPD patients. In addition, oligoclonal expansions lung have observed patients, but overlapping incidence infections, tumors, cigarette smoke exposure obscures antigenic stimulus. We analyzed TCR Vβ repertoire CD4 CD8 purified from lungs spleens mice chronically exposed to...
Abstract Paradigms of eosinophil effector function in the lungs asthma patients invariably depend on activities mediated by cationic proteins released from secondary granules during a process collectively referred to as degranulation. In this study, we generated knockout mice deficient for peroxidase (EPO) assess role(s) abundant granule protein an OVA-challenge model. The loss EPO had no effect development OVA-induced pathologies mouse. absence phenotypic consequences these animals extended...
Bronchitis, asthma, and cystic fibrosis, marked by inflammation mucus hypersecretion, can be caused or exacerbated airway pathogens irritants including acrolein, an aldehyde present in tobacco smoke. To determine whether acrolein inflammatory mediators alter mucin gene expression, steady-state mRNA levels of two mucins, MUC5AC MUC5B, were measured (by RT-PCR) human lung carcinoma cells (NCI-H292). increased after ≥0.01 nM 10 μM prostaglandin E 2 15-hydroxyeicosatetraenoic acid, 1.0 tumor...
Abstract The relationship between eosinophils and the development of Ag-induced pulmonary pathologies, including airway hyper-responsiveness, was investigated using mice deficient for secondary granule component, major basic protein-1 (mMBP-1). loss mMBP-1 had no effect on OVA-induced histopathologies or inflammatory cell recruitment. Lung function measurements knockout demonstrated a generalized hyporeactivity to methacholine-induced airflow changes (relative wild type); however, this...
A strategy to deplete eosinophils from the lungs of ovalbumin (OVA)-sensitized/challenged mice was developed using antibody-mediated depletion. Concurrent administration [viz. peritoneal cavity (systemic) and as an aerosol lung (local)] a rat anti-mouse CCR3 monoclonal antibody resulted in abolition such that airway lumen essentially devoid eosinophils. Moreover, perivascular/peribronchial eosinophil numbers were reduced levels indistinguishable saline-challenged animals. This depletion not...
CD38 controls the chemotaxis of leukocytes to some, but not all, chemokines, suggesting that chemokine receptor signaling in is more diverse than previously appreciated. To determine basis for this heterogeneity, we examined receptors signal a CD38-dependent manner and identified novel “alternative” pathway. Similar “classical” pathway, alternative pathway activated by Gαi2-containing Gi proteins. However, unlike classical also dependent on Gq class G We show Gαq-deficient neutrophils...
Abstract Pseudomonas aeruginosa is a major cause of nosocomial respiratory infections. The eradication P. from the lung involves orchestrated actions pulmonary epithelium and both resident recruited immune cells. NKG2D receptor constitutively expressed on surface circulating tissue-resident NK cells (and other cytotoxic lymphocytes), capable controlling cell activation production cytokines, such as IFN-γ via interactions with ligands stressed Previously, we demonstrated that mediates...
Abstract Chronic obstructive pulmonary disease (COPD) is a debilitating, progressive lung punctuated by exacerbations of symptoms. COPD are most often associated with viral infections, and exposure to cigarette smoke (CS) followed infection has been shown experimentally enhance inflammation, tissue destruction, airway fibrosis. Despite this, however, the cellular mechanisms responsible for this effect unknown. In study, we examined NK cell function in mouse model given vital role cells...
Chronic obstructive pulmonary disease (COPD) is a lethal progressive lung culminating in permanent airway obstruction and alveolar enlargement. Previous studies suggest CTL involvement COPD progression; however, their precise role remains unknown. Here, we investigated whether the activation receptor NK cell group 2D (NKG2D) contributes to development of COPD. Using primary murine epithelium isolated from mice chronically exposed cigarette smoke cultured epithelial cells extract vitro,...
Rationale: Pathogenic T cells drive, or sustain, a number of inflammatory diseases. Chronic obstructive pulmonary disease (COPD) is an lung associated with the accumulation activated cells. We previously demonstrated that chronic cigarette smoke (CS) exposure causes oligoclonal expansion CD4+ and CD8+ in mouse model COPD, thus implicating these pathogenesis.Objectives: To determine whether are pathogenic CS-induced COPD.Methods: transferred CD3+ from filtered air (FA)- CS-exposed mice into...
This study tests the hypothesis that activation of MAPK by physiologically relevant concentrations IL-33 contributes to enhanced cytokine expression IL-12 stimulated human NK cells. While canonically triggers type 2 responses, this can also synergize with 1 cytokines like provoke IFN-γ. We show picogram and are sufficient promote robust secretion IFN-γ cells greatly exceeds resposes either alone. Nanogram doses IL-33, potentially consistent levels in tissue microenvironments, induce...
Acrolein, a low-molecular-weight aldehyde found in photochemical smog and tobacco smoke, can induce mucus hypersecretion, inflammation, airway hyperreactivity. To determine whether changes steady-state mucin gene expression (MUC2 MUC5ac) are associated with histological signs of rats were exposed to acrolein (3.0 parts/million, 6 h/day, 5 days/wk, 2 wk), the trachea main stem bronchi was separated from intrapulmonary airways (lung). The temporal MUC2 MUC5ac mRNA determined by RT-PCR, acidic...
Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous inherited disease causing hypopigmentation and prolonged bleeding times. An additional serious clinical problem of HPS the development lung pathology, which may lead to severe premature death. No cure for exists, previously, no animal model abnormalities has been reported. A mouse HPS, homozygously recessive both Hps1 (pale ear) Hps2 (pearl) genes, exhibits striking type II cells. Type cells lamellar bodies this mutant are...
Eosinophil migration from circulation is controlled, in part, by chemokines through a family of G-protein-coupled chemokine receptors (CCR). Studies human eosinophils have demonstrated that signaling CCR3 prominent pathway leading to chemotaxis, although several other receptor-ligand interactions also appear mediate eosinophil recruitment. The availability genetically unique strains mice permits reductionist approach assess the pathways experimental models disease. However, despite...