A5019357352- Inflammasome and immune disorders
- Extracellular vesicles in disease
- Immune Response and Inflammation
- interferon and immune responses
- Heme Oxygenase-1 and Carbon Monoxide
- Cell death mechanisms and regulation
- Immune Cell Function and Interaction
- MicroRNA in disease regulation
- Pediatric health and respiratory diseases
- Phagocytosis and Immune Regulation
- Kawasaki Disease and Coronary Complications
- Advanced Glycation End Products research
- Adenosine and Purinergic Signaling
- Gout, Hyperuricemia, Uric Acid
- Antimicrobial Peptides and Activities
- Autoimmune and Inflammatory Disorders Research
- Protease and Inhibitor Mechanisms
- Inflammation biomarkers and pathways
- Lymphatic System and Diseases
- Legionella and Acanthamoeba research
- Cystic Fibrosis Research Advances
- Bacillus and Francisella bacterial research
- Research on Leishmaniasis Studies
- Dermatological and COVID-19 studies
- Curcumin's Biomedical Applications
The Ohio State University
2011-2023
Lung Institute
2007-2023
The Ohio State University Wexner Medical Center
2014-2021
Ohio University
2011-2018
Sutter Davis Hospital
2012
Interface (United States)
2009-2010
Indian Institute of Chemical Biology
2001
Abstract Endotoxin administration recapitulates many of the host responses to sepsis. Inhibitors cysteine protease caspase 1 have long been sought as a therapeutic because mice lacking are resistant LPS-induced endotoxic shock. According current thinking, 1-mediated shock requires proinflammatory substrates IL-1β and IL-18. We show, however, that both IL-18 normally susceptible splenocyte apoptosis This finding indicates existence another 1-dependent mediator endotoxemia. Reduced serum high...
Legionella pneumophila (L. pneumophila), the causative agent of a severe form pneumonia called Legionnaires' disease, replicates in human monocytes and macrophages. Most inbred mouse strains are restrictive to L. infection except for A/J, Nlrc4−/− (Ipaf−/−), caspase-1−/− derived Particularly, caspase-1 activation is detected during murine macrophages while absent cells. Recent vitro experiments demonstrate that caspase-7 cleaved by caspase-1. However, biological role downstream not known....
Apoptosis depends upon the activation of intracellular caspases which are classically induced by either an intrinsic (mitochondrial based) or extrinsic (cytokine) pathway. However, in process explaining how endotoxin activated monocytes able to induce apoptosis vascular smooth muscle cells when co-cultured, we uncovered a transcellular inducing pathway that utilizes caspase-1 containing microvesicles. Endotoxin stimulated cell death VSMCs but this activity is found 100,000 g pellets free...
Rationale: Caspase-1 processes interleukin 1β (IL-1β) and IL-18 but may also contribute to apoptosis. In this context, caspase-1 knockout mice have been shown be protected from endotoxin-induced mortality, whereas IL-1β are not protected.Objectives: We therefore sought delineate the mechanisms responsible for differential responses between mice.Methods: knockout, IL-1β/IL-18 double were compared with wild-type survival after intraperitoneal challenge live Escherichia coli.Measurements Main...
Abstract Receptor interacting protein-2 (RIP2) is a caspase recruitment domain (CARD)-containing kinase that interacts with caspase-1 and plays an important role in NF-κB activation. Apoptosis-associated speck-like protein containing CARD (ASC) PYRIN CARD-containing molecule, the induction of apoptosis Although RIP2 has also been linked to activation, knockout animals fail show defect caspase-1-mediated processing proIL-1β its active form. Therefore, function binding remains poorly...
Lung endothelial cell apoptosis and injury occur throughout all stages of acute lung injury/acute respiratory distress syndrome impact disease progression. Caspases 1, 4, 5 are essential for completion the apoptotic program known as pyroptosis that also involves proinflammatory cytokines. Because gasdermin D (GSDMD) mediates pyroptotic death is pore formation, we hypothesized it might direct caspase 1-encapsulated microparticle (MP) release mediate death. Our present work provides evidence...
Rationale: Monocytes are central to the initiation of inflammatory response in sepsis, with caspase-1 activation playing a key role. Monocyte deactivation during sepsis has been linked poor outcomes.Objectives: Given importance immune response, we investigated whether monocytes from patients early septic shock demonstrate alterations mRNAs for caspase-1–related molecules.Methods: Patients (n = 26; age >18 years), critically ill intensive care unit 20), and healthy volunteers 22) were...
Section:ChooseTop of pageAbstract <<MATERIALS AND METHODSRESULTSDISCUSSIONReferencesCITING ARTICLES
Obligate intracellular pathogens such as Leishmania specifically target host phagocytes for survival and replication. Phosphoinositide 3-kinase γ (PI3Kγ), a member of the class I PI3Ks that is highly expressed by leukocytes, controls cell migration initiating actin polymerization cytoskeletal reorganization, which are processes also critical phagocytosis. In this study, we demonstrate IB PI3K, PI3Kγ, plays role in pathogenesis chronic cutaneous leishmaniasis caused L. mexicana . Using...
We have previously shown that critically ill children transfused with red blood cells (RBCs) of longer storage durations more suppressed monocyte function after transfusion compared to fresher RBCs and older stored directly suppress in vitro, through unknown mechanisms. hypothesized RBC-derived microvesicles (MVs) were responsible for suppression.To determine the role RBC unit-derived MVs, we cocultured monocytes supernatants, isolated or supernatants had been depleted MVs from prestorage...
Immune dysregulation during sepsis is poorly understood, however, lymphocyte apoptosis has been shown to correlate with poor outcomes in septic patients. The inflammasome, a molecular complex which includes caspase-1, essential the innate immune response infection and also important induced apoptosis. Our group recently demonstrated that endotoxin-stimulated monocytes release microvesicles (MVs) containing caspase-1 are capable of inducing We sought determine if MVs being released into blood...
Lung endothelial cell apoptosis and injury occurs throughout all stages of acute lung (ALI/ARDS) impacts disease progression. has traditionally been focused on the role neutrophil trafficking to vascular integrin receptors induced by proinflammatory cytokine expression. Although much is known about pathogenesis death in ALI/ARDS, gaps remain our knowledge; as a result which there currently no effective pharmacologic therapy. Enzymes caspases are essential for completion apoptotic program...
Gout is the most prevalent inflammatory arthritis. To study effects of regular physical activity and exercise intensity on inflammation clinical outcome, we examined pathogenesis in an acute model murine gout analyzed human patient data as a function activity.NF-κB-luciferase reporter mice were organized into four groups exercised at 0 m/min (non-exercise), 8 (low-intensity), 11 (moderate-intensity), 15 (high-intensity) for two weeks. Mice subsequently received intra-articular monosodium...
Background Thrombospondin-1 (TSP-1) is involved in many biological processes, including immune and tissue injury response, but its role sepsis unknown. Cell surface expression of TSP-1 on platelets increased could activate the anti-inflammatory cytokine transforming growth factor beta (TGFβ1) affecting outcome. Because these observations we sought to determine importance sepsis. Methodology/Principal Findings We performed studies null wild type (WT) C57BL/6J mice utilized cecal ligation...
Abstract Macrophages mediate crucial innate immune responses via caspase-1-dependent processing and secretion of IL-1β IL-18. While wild type Salmonella typhimurium infection is lethal to mice, a strain that persistently expresses flagellin was cleared by the cytosolic detection pathway NLRC4 activation caspase-1; however, this clearance independent Instead, caspase-1 induced pyroptotic cell death released bacteria from macrophages, exposing them uptake killing reactive oxygen species in...
Abstract TLRs, a family of membrane-bound pattern recognition receptors found on innate immune cells, have been well studied in the context cancer therapy. Activation these has shown to induce inflammatory anticancer events, including differentiation and apoptosis, across wide variety malignancies. In contrast, intracellular such as NOD-like minimally studied. NOD2 is member receptor that initiates signaling response bacterial motif muramyl dipeptide. this study, we examined influence human...
The key to further improving outcomes in sepsis lies understanding and abrogating the dysfunctional immune response that leads organ failure. Activation of gasdermin-D, a pore-forming protein within inflammasome cascade, has recently been recognized as critical step pyroptosis dysfunction. In this study, we sought investigate presence gasdermin-D critically ill subjects.Prospective pilot study comparing microparticulate active levels patients admitted medical ICU at Ohio State University...