A5080828590- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Occupational and environmental lung diseases
- Neonatal Respiratory Health Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Pulmonary Hypertension Research and Treatments
- Autophagy in Disease and Therapy
- Air Quality and Health Impacts
- Occupational exposure and asthma
- Bone and Dental Protein Studies
- Hedgehog Signaling Pathway Studies
- Medical Imaging and Pathology Studies
- Respiratory Support and Mechanisms
- Pleural and Pulmonary Diseases
- Selenium in Biological Systems
- Heavy Metal Exposure and Toxicity
- Peroxisome Proliferator-Activated Receptors
- ATP Synthase and ATPases Research
- Inflammation biomarkers and pathways
- Advanced Glycation End Products research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Hydrogen's biological and therapeutic effects
- Eosinophilic Disorders and Syndromes
- Adipose Tissue and Metabolism
- Fatty Acid Research and Health
University of Alabama at Birmingham
2016-2025
Pulmonary and Allergy Associates
2018-2019
University of Iowa
2015
Carver Bible College
2014
University of North Dakota
2010-2011
Alternative activation of alveolar macrophages is linked to fibrosis following exposure asbestos. The scavenger receptor, macrophage receptor with collagenous structure (MARCO), provides innate immune defense against inhaled particles and pathogens; however, a for asbestos has not been identified. We hypothesized that MARCO acts as an initial signaling asbestos, polarizes profibrotic M2 phenotype, required the development asbestos-induced fibrosis. Compared normal subjects, isolated from...
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with an increased mortality. Metabolic reprogramming has critical role in multiple chronic diseases. Lung macrophages expressing the mitochondrial calcium uniporter (MCU) have fibrotic repair, but contribution of MCU macrophage metabolism not known. Here, we show that regulates peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and metabolic to fatty acid oxidation (FAO) macrophages. regulated PGC-1α...
Mitochondrial dysfunction has been associated with age-related diseases, including idiopathic pulmonary fibrosis (IPF). We provide evidence that implicates chronic elevation of the mitochondrial anion carrier protein, uncoupling protein-2 (UCP2), in increased generation reactive oxygen species, altered redox state and cellular bioenergetics, impaired fatty acid oxidation, induction myofibroblast senescence. This pro-oxidant senescence reprogramming occurs concert conventional actions UCP2 as...
M2 macrophages are implicated in the development of pulmonary fibrosis as they generate profibrotic signals. The polarization process, at least part, is regulated by epigenetic modulation. Because Cu,Zn-superoxide dismutase-induced H2O2 can polarize to a phenotype, we hypothesized that modulation redox state cell involved macrophage phenotype. In this study, show signal transducer and activator transcription 6 (STAT6) regulates Jumonji domain containing (Jmjd) 3, histone H3 lysine 27...
Macrophage activation is implicated in the development of pulmonary fibrosis by generation profibrotic molecules. Although NADPH oxidase 4 (NOX4) known to contribute fibrosis, its effects on macrophage and mitochondrial redox signaling are unclear. Here, we show that NOX4 crucial for lung polarization fibrotic repair after asbestos exposure. was elevated macrophages from subjects with asbestosis, mice harboring a deletion were protected asbestos-induced fibrosis. promoted increased...
The mitochondrial calcium uniporter (MCU) regulates metabolic reprogramming in lung macrophages and the progression of pulmonary fibrosis. Fibrosis is associated with apoptosis resistance macrophages; however, mechanism(s) by which occurs poorly understood. Here, we found a marked increase B-cell lymphoma-2 (Bcl-2) from subjects idiopathic fibrosis (IPF). Similar findings were seen bleomycin-injured wild-type (WT) mice, whereas Bcl-2 was markedly decreased mice expressing dominant-negative...
Asbestosis is a prototypical type of fibrosis that progressive and does not resolve. ER stress increased in multiple cell types contribute to fibrosis; however, the mechanism(s) by which lung macrophages contributes poorly understood. Here, we show resulted PERK activation human subjects with asbestosis. Similar results were seen asbestos-injured mice. Mice harboring conditional deletion Eif2ak3 protected from fibrosis. Lung asbestosis had evidence metabolic reprogramming fatty acid...
Fibrosis in multiple organs, including the liver, kidney, and lung, often occurs secondary to environmental exposure. Asbestos exposure is one important cause of lung fibrosis. The mechanisms that mediate fibrosis not fully understood, although mitochondrial oxidative stress alveolar macrophages critical for development. Mitochondrial Ca2+ levels can be associated with production reactive oxygen species. Here, we show patients asbestosis have higher compared normal patients. calcium...
Although the mechanisms for fibrosis development remain largely unknown, recent evidence indicates that endoplasmic reticulum (ER) stress and activation of unfolded protein response (UPR) may act as an important fibrotic stimulus in diseased lungs. ER is observed lungs patients with idiopathic pulmonary fibrosis. In this study we evaluated if UPR was present macrophages exposed to chrysotile asbestos associated asbestos-induced Macrophages had elevated transcript levels several genes. loaded...
Heavy metals released into the environment have a significant effect on respiratory health. Lung macrophages are important in mounting an inflammatory response to injury, but they also involved repair of injury. Macrophages develop mixed phenotypes complex pathological conditions and polarize predominant phenotype depending duration stage injury and/or repair. Little is known about reprogramming required for lung switch between these divergent functions; therefore, understanding mechanism(s)...
Emerging data indicate an association between environmental heavy metal exposure and lung disease, including lower respiratory tract infections (LRTIs). Here, we show by single-cell RNA sequencing increase in Pparg gene expression macrophages from mice exposed to cadmium and/or infected with Streptococcus pneumoniae. However, the or infection mediated inhibitory posttranslational modification of peroxisome proliferator-activated receptor γ (PPARγ) exacerbate LRTIs. Cadmium increased ERK...
Macrophages are important in mounting an innate immune response to injury as well repair of injury. Gene expression Rho proteins is known be increased fibrotic models; however, the role these idiopathic pulmonary fibrosis (IPF) not known. Here, we show that BAL cells from patients with IPF have a profibrotic phenotype secondary activation small GTPase Rac1. Rac1 requires posttranslational modification, geranylgeranylation, C-terminal cysteine residue. We found by supplying more substrate for...
Background: Alveolar macrophages (AMs) are resident inflammatory cells in the lung that serve as early sentinels of infection or injury. We have identified thioredoxin reductase 1 inhibition by gold compounds increases activation nuclear factor erythroid 2-related 2 (NRF2)-dependent pathways to attenuate responses. The present studies utilized murine alveolar (MH-S) test hypothesis compound, auranofin (AFN), decreases interleukin (IL)-1β expression through NRF2-mediated interactions with...
Pulmonary fibrosis is a progressive lung disease often occurring secondary to environmental exposure. Asbestos exposure an important mediator of and remains significant cause despite strict regulations limit Lung macrophages play integral role in the pathogenesis induced by asbestos (asbestosis), part generating reactive oxygen species (ROS) promoting resistance apoptosis. However, mechanism which acquire apoptosis not known. Here, we confirm that isolated from asbestosis subjects are...
Cigarette smoking is prevalent in the United States and leading cause of preventable diseases. A prominent complication an increase lower respiratory tract infections (LRTIs). Although LRTIs are known to be increased subjects that smoke, mechanism(s) by which this occurs poorly understood.Determine how cigarette smoke (CS) reduces reactive oxygen species (ROS) production phagocytic NOX2 (NADPH oxidase 2), essential for innate immunity lung macrophages.NOX2-derived ROS Rac2 (Ras-related C3...
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease associated with mitochondrial oxidative stress. Mitochondrial reactive oxygen species (mtROS) are important for cell homeostasis by regulating dynamics. Here, we show that IPF BAL cells exhibited increased biogenesis is, in part, due to nuclear expression of peroxisome proliferator-activated receptor-ɣ (PPARɣ) coactivator (PGC)-1α. Increased PPARGC1A mRNA directly correlated reduced function subjects. Oxidant-mediated...