A5064167863- Diabetes and associated disorders
- Pancreatic function and diabetes
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Diabetes Management and Research
- Endoplasmic Reticulum Stress and Disease
- Advanced Glycation End Products research
- Heme Oxygenase-1 and Carbon Monoxide
- Cannabis and Cannabinoid Research
- Adipose Tissue and Metabolism
- Phagocytosis and Immune Regulation
- Immune cells in cancer
- Adipokines, Inflammation, and Metabolic Diseases
- Metabolism, Diabetes, and Cancer
- Aquaculture disease management and microbiota
- Adenosine and Purinergic Signaling
- Porphyrin and Phthalocyanine Chemistry
- Immunotherapy and Immune Responses
- Calcium signaling and nucleotide metabolism
- FOXO transcription factor regulation
- Liver Disease Diagnosis and Treatment
- Peroxisome Proliferator-Activated Receptors
- Cancer, Hypoxia, and Metabolism
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Extracellular vesicles in disease
Indiana University School of Medicine
2024-2025
Indiana University – Purdue University Indianapolis
2024-2025
Children's Hospital of Pittsburgh
2015-2024
Indiana University
2024
University of Pittsburgh Medical Center
2014-2024
University School
2024
University of Pittsburgh
2014-2023
Tangshan Gongren Hospital
2011
Duke Medical Center
2011
Duke University Hospital
2011
Abstract Steroid-resistant asthma comprises an important source of morbidity in patient populations. TH17 cells represent a distinct population CD4+ Th that mediate neutrophilic inflammation and are characterized by the production IL-17, IL-22, IL-6. To investigate function context Ag-induced airway inflammation, we polarized naive T from DO11.10 OVA-specific TCR-transgenic mice to TH2 or phenotype culturing conditioned medium. In addition, also tested steroid responsiveness cells. vitro,...
The process of human islet isolation triggers a cascade stressful events in the islets Langerhans involving activation apoptosis and necrosis production proinflammatory molecules that negatively influence yield function may produce detrimental effects after transplantation. In this study, we showed nuclear factor-kappaB (NF-kappaB) poly(ADP-ribose) polymerase (PARP), two major pathways responsible for cellular responses to stress, already occurs pancreatic cells during procedure....
We present here the first report of a metalloporphyrin-based antioxidant that can prevent or delay onset autoimmune diabetes. Type 1 diabetes is an process whereby T-cells recognize pancreatic β-cell antigens and initiate leukocyte infiltrate produces proinflammatory cytokines reactive oxygen species (ROS), ultimately leading to destruction. Because islet β-cells have reduced capacity scavenge free radicals, they are very sensitive ROS action. Metalloporphyrin-based superoxide dismutase...
At this time, the only definitive treatment of hepatic failure is liver transplantation. However, transplantation has been limited by severely supply human donor livers. Alternatively, a regenerative medicine approach recently proposed in rodents that describe production three-dimensional whole-organ scaffolds for assembly engineered complete organs. In present study, we decellularization porcine livers to generate constructs at scale can be clinically relevant. Adult ischemic were...
OBJECTIVE Macrophages play an important role in the pathogenesis of insulin resistance via production proinflammatory cytokines. Our goal is to decipher molecular linkage between cytokine and macrophages. RESEARCH DESIGN AND METHODS We determined profiles cultured macrophages identified interleukin (IL)-1β gene as a potential target FoxO1, key transcription factor that mediates action on expression. studied mechanism by which FoxO1 insulin-dependent regulation IL-1β expression correlated...
The generation of the pro-inflammatory cytokines IL-6, TNF-α, and IL-1β fuel acute phase response (APR). To maintain body homeostasis, increase inflammatory proteins is resolved by via presently unknown mechanisms. Hepatocyte growth factor (HGF) transcribed in to IL-6. Since IL-6 production promotes HGF induces APR, we posited that accumulating might be a likely candidate for quelling excess inflammation under non-pathological conditions. We sought assess role how it influences regulation...
Reactive oxygen species are used by the immune system to eliminate infections; however, they may also serve as signaling intermediates coordinate efforts of innate and adaptive systems. In this study, we show that eliminating macrophage T cell superoxide production through NADPH oxidase (NOX), polarization was altered. After stimulation with immobilized anti-CD3 anti-CD28 or priming recall, cells from NOX-deficient mice exhibited a skewed Th17 phenotype, whereas NOX-intact produced cytokines...
Redox reactions are imperative to preserving cellular metabolism yet must be strictly regulated. Imbalances between reactive oxygen species (ROS) and antioxidants can initiate oxidative stress, which without proper resolve, manifest into disease. In type 1 diabetes (T1D), T-cell-mediated autoimmune destruction of pancreatic β-cells is secondary the primary invasion macrophages dendritic cells (DCs) islets. Macrophages/DCs, however, activated by intercellular ROS from resident phagocytes...
T cells are strongly regulated by oxidizing environments and amino acid restriction. How reprogram metabolism to adapt these extracellular stress situations is not well understood. Here, we show that starvation induce ATF4 in CD4
Background Type 1 Diabetes (T1D) is caused by a combination of genetic and environmental factors that trigger autoimmune-mediated destruction pancreatic β-cells. Defects in β-cell stress response pathways such as autophagy may play an important role activating and/or exacerbating the immune disease development. Previously, we discovered impaired prior to onset T1D, implicating this pathway T1D pathogenesis. Aims To assess health survival, whether defects render islets more immunogenic....
The most commonly used technical approach to isolate human pancreatic islets intended for allotransplants generates a product that is hampered by mechanical and chemical insults, which dramatically reduce the mass of viable functional transplantable cells. We tested novel class antioxidant compounds (SOD mimics: AEOL10113 AEOL10150) protect from oxidative stress in order improve preservation isolated tissue. Addition SOD mimic culture, after isolation, allowed survival significantly higher...
Abstract Chronic ethanol (EtOH) abuse results in the development of steatosis, alcoholic hepatitis, and cirrhosis. Augmented TNF-α production by macrophages Kupffer cells signaling via p55 TNF receptor have been shown to be critical for these effects chronic EtOH; however, molecular mechanisms leading augmented remain unclear. Using cell culture models vivo studies we demonstrate that EtOH increased transcription, which is independent NF-κB. reporter assays chromatin immunoprecipitation...
Stem cells are classically defined by their multipotent, long-term proliferation, and self-renewal capabilities. Here, we show that increased antioxidant capacity represents an additional functional characteristic of muscle-derived stem (MDSCs). Seeking to understand the superior regenerative MDSCs compared with myoblasts in cardiac skeletal muscle transplantation, our group hypothesized survival oxidative inflammatory stress inherent transplantation may play important role. Evidence...
The role of reactive oxygen species (ROS) and their dissipation in type 1 diabetes pathogenesis have garnered considerable controversy. Our recent work has demonstrated the importance NADPH oxidase (NOX) activity for development modulating T-cell autoreactivity. We previously linked decreased monocyte ROS with resistance alloxan-resistant mouse, NOD-Ncf1(m1J) mice a genetic ablation NOX had reduced delayed compared NOD mice.To determine required cellular sources that are necessary...
The immune system is necessary for protecting against various pathogens. However, under certain circumstances, self-reactive cells can drive autoimmunity, like that exhibited in type 1 diabetes (T1D). CD4+ T are major contributors to the immunopathology T1D, and order optimal cell activation, third signal reactive oxygen species (ROS) must be present. role ROS play mediating this process remains further understood. Recently, cellular metabolic programs have been shown dictate function fate...
In spite of tolerance mechanisms, some individuals develop T-cell–mediated autoimmunity. Posttranslational modifications that increase the affinity epitope presentation and/or recognition represent one means through which self-tolerance mechanisms can be circumvented. We investigated T-cell peptides correspond to modified β-cell antigens in subjects with type 1 diabetes. Modified elicited enhanced proliferation by autoreactive clones. Endoplasmic reticulum (ER) stress insulinoma cells...
Lymphocyte activation gene-3 (LAG-3) is an inhibitory receptor expressed by CD4+ T cells and tempers their homeostatic expansion. Because cell proliferation tightly coupled to bioenergetics, we investigate the role of LAG-3 in modulating naive metabolism. deficiency enhances metabolic profile elevating levels mitochondrial biogenesis. In vivo, blockade partially restores expansion phenotype wild-type Lag3-/- cells, solidifying that controls these processes. also demonstrate greater signal...