A5046568943- Inflammasome and immune disorders
- Autophagy in Disease and Therapy
- Alzheimer's disease research and treatments
- Cystic Fibrosis Research Advances
- Neuroinflammation and Neurodegeneration Mechanisms
- Vibrio bacteria research studies
- MicroRNA in disease regulation
- COVID-19 Clinical Research Studies
- Immune Response and Inflammation
- Asthma and respiratory diseases
- Axial and Atropisomeric Chirality Synthesis
- Coordination Chemistry and Organometallics
- Renal Diseases and Glomerulopathies
- Analytical Chemistry and Chromatography
- Chemical synthesis and alkaloids
- Cell death mechanisms and regulation
- Heme Oxygenase-1 and Carbon Monoxide
- Systemic Lupus Erythematosus Research
- Phagocytosis and Immune Regulation
- Chemical Reaction Mechanisms
- Antibiotic Resistance in Bacteria
- Pancreatitis Pathology and Treatment
- S100 Proteins and Annexins
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Legionella and Acanthamoeba research
The Ohio State University
2017-2024
Assiut University
1972-2022
Mansoura University
2022
The Ohio State University Wexner Medical Center
2019
Lung Institute
2017
Columbus Center
2017
Significance We report the discovery of fundamental roles for noncanonical inflammasome molecule Caspase-4/11 in promoting pathological inflammatory and prothrombotic pathways severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) infections. Our work demonstrates that Caspase-11 has a broader role immune responses beyond its previously appreciated effects bacterial Further, we show Caspase-11–deficient mice infected with SARS–CoV-2 fare significantly better terms overall illness, lung...
Gout is characterized by attacks of arthritis with hyperuricemia and monosodium urate (MSU) crystal-induced inflammation within joints. Innate immune responses are the primary drivers for tissue destruction in gout. MSU crystals engage Nlrp3 inflammasome leading to activation caspase-1 production IL-1β IL-18 gout-affected joints, promoting influx neutrophils monocytes. Here we show that caspase-11-/- mice their derived macrophages produce significantly reduced levels gout-specific cytokines...
Autophagy is a proposed route of amyloid-β (Aβ) clearance by microglia that halted in Alzheimer's Disease (AD), though mechanisms underlying this dysfunction remain elusive. Here, primary from adult AD (5xFAD) mice were utilized to demonstrate 5xFAD fail degrade Aβ and express low levels autophagy cargo receptor NBR1. In mouse brains, we show for the first time elevated microRNA cluster Mirc1/Mir17-92a, which known downregulate proteins. By situ hybridization post-mortem human tissue...
ABSTRACT CASP4/caspase-11-dependent inflammasome activation is important for the clearance of various Gram-negative bacteria entering host cytosol. Additionally, CASP4 modulates actin cytoskeleton to promote maturation phagosomes harboring intracellular pathogens such as Legionella pneumophila but not those enclosing nonpathogenic bacteria. Nevertheless, this non-inflammatory role regarding trafficking vacuolar remains poorly understood. Macroautophagy/autophagy, a catabolic process within...
Alzheimer's disease (AD) is the sixth leading cause of death in USA. It established that neuroinflammation contributes to synaptic loss, neuronal death, and symptomatic decline AD patients. Accumulating evidence suggests a critical role for microglia, innate immune phagocytes brain. For instance, microglia release pro-inflammatory products such as IL-1β which highly implicated pathobiology. The mechanisms underlying transition proinflammatory promoters remain largely unknown. To address this...
Burkholderia cenocepacia (B. cenocepacia) is an opportunistic bacterium; causing severe life threatening systemic infections in immunocompromised individuals including cystic fibrosis patients. The lack of gasdermin D (GSDMD) protects mice against endotoxin lipopolysaccharide (LPS) shock. On the other hand, GSDMD promotes survival response to certain bacterial infections. However, role during B. infection not yet determined. Our vitro study shows that restricts replication within macrophages...
Article21 October 2019Open Access Transparent process Caspase-11 counteracts mitochondrial ROS-mediated clearance of Staphylococcus aureus in macrophages Kathrin Krause Department Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State University, Columbus, OH, USA Search for more papers by this author Kylene Daily Shady Estfanous Kaitlin Hamilton Asmaa Badr Arwa Abu Khweek Biology Biochemistry, Birzeit Birzeit, West Bank, Palestine Rana Hegazi Midhun NK Anne Brett Klamer...
Cystic fibrosis (CF) human and mouse macrophages are defective in their ability to clear bacteria such as
Autophagy is a highly regulated, biological process that provides energy during periods of stress and starvation. This conserved also acts as defense mechanism clears microbes from the host cell. impaired in Cystic Fibrosis (CF) patients CF mice, their cells exhibit low expression levels essential autophagy molecules. The genetic disorder due to mutations cystic fibrosis transmembrane conductance regulator (cftr) gene encodes for chloride channel. are particularly prone infection by...
Neuroinflammation and accumulation of Amyloid Beta (Aβ) accompanied by deterioration special memory are hallmarks Alzheimer's disease (AD). Effective preventative treatment options for AD still needed. Microglia in brains characterized elevated levels microRNA-17 (miR-17), which is defective autophagy, Aβ accumulation, increased inflammatory cytokine production. However, the effect targeting miR-17 on pathology loss not clear. To specifically inhibit microglia, we generated mannose-coated...
Abstract Neuroinflammation is a hallmark of Alzheimer’s disease (AD) pathobiology. Microglia in AD brains show elevated levels microRNA-17 (miR-17), which maintains balance between pro- and anti-inflammatory cytokine production. play an essential role the production cytokines; however, microglial miR-17 controlling neuroinflammation not clear. We hypothesized that targeting microglia vivo will decrease dampen immune cell activation, reducing amyloid beta (Aβ) deposition preventing behavioral...
BackgroundMitochondria play a key role in immune defense pathways, particularly for macrophages. We and others have previously demonstrated that cystic fibrosis (CF) macrophages exhibit weak autophagy activity exacerbated inflammatory responses. Previous studies revealed mitochondria are defective CF epithelial cells, but to date, the connection between mitochondrial function macrophage dysregulation has not been fully elucidated. Here, we present characterization of dysfunction...
To evaluate the renal resistive index (RI) in lupus nephritis (LN) patients and to study its association with clinical features, laboratory investigations LN pathological classes systemic erythematosus (SLE) patients. The included 45 SLE 25 matched controls. disease activity (SLEDAI) was assessed subdivided into (renal SLEDAI ≥ 4) no-renal (NRA) = 0). Ultrasound Doppler examination done measure RI. Renal biopsies were performed 30 mean age of 29.8 ± 10.1 years duration 4.3 3.9 years. They 40...
Abstract Alzheimer’s Disease (AD) is the 6th leading cause of death in US. It established that neuroinflammation contributes to synaptic loss, neuronal death, and symptomatic decline AD patients. Accumulating evidence suggests a critical role for microglia, innate immune phagocytes brain. For instance, microglia release pro-inflammatory products such as IL-1β which highly implicated pathobiology. The mechanisms underlying transition proinflammatory promoters remain largely unknown. To...
Abstract SARS-CoV-2 is a worldwide health concern, and new treatment strategies are needed 1 . Targeting inflammatory innate immunity pathways holds therapeutic promise, but effective molecular targets remain elusive. Here, we show that human caspase-4 (CASP4), its mouse homologue, caspase-11 (CASP11), upregulated in infections, CASP4 expression correlates with severity of infection humans. SARS-CoV-2-infected Casp11 -/- mice were protected from severe weight loss lung pathology, including...
To measure the levels of serum calprotectin (CLP) in rheumatoid arthritis (RA) and osteoarthritis (OA) patients to assess its association with disease activity, severity functional status. A total 30 RA and30 OA controlswere included. Rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), Disease activity score (DAS28), health assessment questionnaire (HAQ) medical records-based index (RARBIS) were assessed patients. Western Ontario McMaster Osteoarthritis (WOMAC)...
An amendment to this paper has been published and can be accessed via a link at the top of paper.
Abstract Asthma is an inflammatory lung disorder characterized by mucus hypersecretion, cellular infiltration, and bronchial hyper-responsiveness. House dust mites (HDM) are the most prevalent cause of allergic sensitization. Canonical noncanonical inflammasomes multiprotein complexes that assemble in response to pathogen or danger-associated molecular patterns (PAMPs DAMPs). Murine caspase-11 engages inflammasome. We addressed role mediating host responses HDM subsequent inflammation using...