A5081642385- Immune Response and Inflammation
- Hepatitis B Virus Studies
- Cholesterol and Lipid Metabolism
- Lipid metabolism and biosynthesis
- Cancer, Lipids, and Metabolism
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Pancreatitis Pathology and Treatment
- Drug Transport and Resistance Mechanisms
- Metabolism and Genetic Disorders
- Sepsis Diagnosis and Treatment
- Peroxisome Proliferator-Activated Receptors
- Heat shock proteins research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Lipoproteins and Cardiovascular Health
- Inflammation biomarkers and pathways
- Immune cells in cancer
- Endoplasmic Reticulum Stress and Disease
- Pharmacogenetics and Drug Metabolism
- HIV Research and Treatment
- Bacteriophages and microbial interactions
- Lipid Membrane Structure and Behavior
- Atherosclerosis and Cardiovascular Diseases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Neonatal Respiratory Health Research
National Institutes of Health Clinical Center
2012-2025
National Institutes of Health
2000-2023
Pirogov Russian National Research Medical University
2022
National Heart Lung and Blood Institute
2000-2016
Nova Institut
2013-2016
National Institute of Diabetes and Digestive and Kidney Diseases
2011
Center for Clinical Research (United States)
2006-2008
Cardinal Glennon Children’s Medical Center
2004
Center for Biologics Evaluation and Research
2001-2002
Ministry of Health of the Russian Federation
1998
Serum amyloid A protein (SAA) is an acute-phase reactant, known to mediate pro-inflammatory cellular responses. This study reports that CLA-1 (CD36 and LIMPII Analogous-1; human orthologue of the Scavenger Receptor Class B Type I (SR-BI)) mediates SAA uptake downstream signaling. Flow cytometry experiments revealed more than a 5-fold increase Alexa-488 in HeLa cells stably transfected with CLA-1. Alexa 488-HDL directly correlated when determined several cell clones expressing various levels...
Abstract Scavenger receptor CD36 mediates Staphylococcus aureus phagocytosis and initiates TLR2/6 signaling. We analyzed the role of in uptake TLR-independent signaling various bacterium, including Escherichia coli, Klebsiella pneumoniae, Salmonella typhimurium, S. aureus, Enterococcus faecalis. Expression human HeLa cells increased both Gram-positive Gram-negative bacteria compared with control mock-transfected cells. Bacterial adhesion was associated pathogen phagocytosis. Upon...
Scavenger receptor, class B, type I (SR-BI) mediates selective uptake of high density lipoprotein (HDL) cholesteryl ester. SR-BI recognizes HDL, low (LDL), exchangeable apolipoproteins, and protein-free lipid vesicles containing negatively charged phospholipids. Lipopolysaccharides (LPS) are highly glycosylated anionic phospholipids contributing to septic shock. Despite significant structural similarities between LPS, the role in LPS is unknown. Cla-1, human orthologue, was determined be a...
ABSTRACT Lipopolysaccharide (LPS) has recently been shown to facilitate macrophage foam cell formation and suggested be a proatherogenic factor. The mechanism of LPS induced cholesterol accumulation, however, is unclear. In this report, using the macrophage-like RAW 264.7 line, we provide experimental evidence that LPS's effects may at least in part reflect altered metabolism. Data presented demonstrate dose-dependent manner, able down regulate mRNA expression two primary high-density...
Serum amyloid A (SAA) is a major acute phase protein involved in multiple physiological and pathological processes. This study provides experimental evidence that CD36, phagocyte class B scavenger receptor, functions as novel SAA receptor mediating proinflammatory activity. The uptake of Alexa Fluor® 488 well other established CD36 ligands was increased 5–10-fold HeLa cells stably transfected with when compared mock-transfected cells. Unlike apolipoproteins bind to only induced 10–50-fold...
Chronic kidney disease (CKD) is associated with persistent low-grade inflammation and immunosuppression. In this study we tested the role of Toll-like receptor 4, main for endotoxin (LPS), in a mouse model renal fibrosis progressive CKD that better resembles human disease. C3HeJ (TLR4 mutant) mice have missense point mutation TLR4 gene, rendering nonfunctional. after folic acid injection, mutant developed less interstititial comparison to wild-type (WT) mice. Furthermore, 4 weeks 5/6...
Human familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is characterized by low HDL, accumulation of an abnormal cholesterol-rich multilamellar particle called lipoprotein-X (LpX) in plasma, and renal disease. The aim our study was to determine if LpX nephrotoxic gain insight into the pathogenesis FLD We administered a synthetic LpX, nearly identical endogenous its physical, chemical biologic characteristics, wild-type Lcat-/- mice. Our vitro vivo studies demonstrated...
Abstract Class B scavenger receptors (SR-B) are lipoprotein that also mediate pathogen recognition, phagocytosis, and clearance as well pathogen-induced signaling. In this study we report three members of the SR-B family, namely, CLA-1, CLA-2, CD36, recognition bacteria not only through interaction with cell wall LPS but cytosolic chaperonin 60. HeLa cells stably transfected any these SR-Bs demonstrated markedly (3- to 5-fold) increased binding endocytosis Escherichia coli, LPS, 60 (GroEL)...
Abstract Class B scavenger receptors (SR-Bs), such as SR-BI/II or CD36, bind lipoproteins but also mediate bacterial recognition and phagocytosis. In evaluating whether blocking can prevent intracellular proliferation, phagocyte cytotoxicity, proinflammatory signaling in infection/sepsis, we found that SR-BI/II– CD36-deficient phagocytes are characterized by a reduced survival lower cytokine response were protected from cytotoxicity the presence of antibiotics. Mice deficient either CD36...
Abstract The class B scavenger receptors BI (SR-BI) and BII (SR-BII) are high-density lipoprotein that recognize various pathogens, including bacteria their products. It has been reported SR-BI/II null mice more sensitive than normal to endotoxin-induced inflammation sepsis. Because the knockout model demonstrates multiple immune metabolic disorders, we investigated role of each receptor in LPS-induced inflammatory response tissue damage using transgenic with pLiv-11–directed expression...
ABSTRACT APOBEC3 proteins (A3s) play an important role in host innate immunity against viruses and DNA mutations cancer. A3s-induced both viral human genomes vary significantly from non-lethal to localized hypermutations, such as kataegis How A3s are regulated remains largely unknown. Since exist complexes belong the same family APOBEC-1 (A1), which requires cofactors be functional, we investigated of A1 other A3 potentially associated hnRNPs on mutational activity using hepatitis B virus...
CD36 and LIMPII analog 1, CLA-1, its splicing variant, CLA-2 (SR-BI SR-BII in rodents), are human high density lipoprotein receptors with an identical extracellular domain which binds a spectrum of ligands including bacterial cell wall components. In this study, CLA-1- CLA-2-stably transfected HeLa HEK293 cells demonstrated several-fold increases the uptake various bacteria over mock-transfected cells. All tested, both Gram-negatives (Escherichia coli K12, K1 Salmonella typhimurium)...
Human scavenger receptor class B type I, CLA-1, mediates lipopolysaccharide (LPS) binding and internalization (Vishnyakova, T. G., Bocharov, A. V., Baranova, I. N., Chen, Z., Remaley, T., Csako, Eggerman, L., Patterson, P. (2003) J. Biol. Chem. 278, 22771–22780). Because one of the recognition motifs in SR-B1 ligands is anionic amphipathic α-helix, we analyzed effects model α-helical-containing peptides on LPS uptake LPS-stimulated cytokine production. The L-37pA peptide, containing two A...
Abstract Synthetic amphipathic helical peptides (SAHPs) designed as apolipoprotein A-I mimetics are known to bind class B scavenger receptors (SR-Bs), SR-BI, SR-BII, and CD36, that mediate lipid transport facilitate pathogen recognition. In this study, we evaluated SAHPs, selected for targeting human by their ability attenuate LPS-induced inflammation, endothelial barrier dysfunction, acute lung injury (ALI). L37pA, which targets CD36 SR-BI equally, inhibited IL-8 secretion dysfunction in...
Apolipoprotein B mRNA-editing enzyme catalytic subunit 3 (APOBEC-3) enzymes are cytidine deaminases that broadly and constitutively expressed. They often up-regulated during carcinogenesis candidate genes for causing the major single-base substitution in cancer-associated DNA mutations. Moreover, APOBEC-3s involved host innate immunity against many viruses. However, how APOBEC-3 mutational activity is regulated normal pathological conditions remains largely unknown. Heat shock protein levels...
APOBEC-1 overexpression in liver has been shown to effectively reduce apoB-100 levels. However, nonspecific hypermutation and tumor formation potentially related transgenic animals compromise its potential use for gene therapy. In studying apoB mRNA editing regulation, we found that the core auxiliary factor ACF dose-dependently increases specific with variable site sensitivity. Overexpression of together human hepatic HepG2 cells hypermutated mRNAs 20%-65% at sites 6639, 6648, 6655, 6762,...
Serum amyloid A (SAA) is an acute phase protein with cytokine-like and chemotactic properties, that markedly up-regulated during various inflammatory conditions. Several receptors, including FPRL-1, TLR2, TLR4, RAGE, class B scavenger SR-BI CD36, have been identified as SAA receptors. This study provides new evidence SR-BII, splice variant of SR-BI, could function receptor mediating its uptake pro-inflammatory signaling. The Alexa Fluor488 was (~3 fold) increased in hSR-BII-expressing HeLa...
Oxidized apolipoprotein B (oxLDL) and oxidized ApoA-I (oxHDL) are proatherogenic. Their prognostic value for assessing high-risk plaques by coronary computed tomography angiography (CCTA) is missing.In a prospective, observational study, 306 participants with cardiovascular disease (CVD) had extensive lipoprotein profiling. Proteomics analysis was performed on isolated oxHDL, atherosclerotic plaque assessment accomplished quantitative CCTA.Patients were predominantly White, overweight men...
The class B scavenger receptor CD36 is known to bind and mediate the transport of lipid-related ligands it functions as a pattern recognition (PRR) for variety pathogens, including bacteria viruses. In this study, we assessed CD36's role PRR mediating pro-inflammatory effects several Danger-Associated Molecular Patterns (DAMPs) used either single preparation or combination DAMPs in form total cell/skeletal muscle tissue lysates. Our data demonstrated that multiple DAMPs, HMGB1, HSPs, histone...
APOBEC3s are innate single-stranded DNA cytidine-to-uridine deaminases that catalyze mutations in both pathogen and human genomes with significant roles disease. However, how mutate a is available momentarily during transcription or replication vivo remains relatively unknown. In this study, utilizing hepatitis B virus (HBV) viral mutations, we evaluated the mutational characteristics of individual reference to HBV process through whole single-strand (-)-DNA genome mutation analyses. We...
A new human 95 kDa high density lipoprotein (HDL)-binding protein (HBP) corresponding to a affinity HDL-binding site with Kd = 1.67 μg/mL and capacity of 13.4 ng/mg was identified in fetal hepatocytes. The HDL binding the HBP plateaus at 2.5−5 under reducing nonreducing conditions. association HDL3 plateaued 15−30 min while dissociation complete 30 min. HDL3, apoA-I, apoA-II were recognized by low lipoproteins (LDL) tetranitromethane-modified not. predominantly resides on surface cells since...
Recent studies suggest an anti-inflammatory protective role for class B scavenger receptor BI (SR-BI) in endotoxin-induced inflammation and sepsis. Other data, including ours, provide evidence alternative of SR-BI, facilitating bacterial endotoxin uptake contributing to infection. Enhanced susceptibility SR-BI-deficient mice due their glucocorticoid deficiency complicates the understanding SR-BI's endotoxemia/sepsis, calling use models. In this study, using human SR-BI (hSR-BI) hSR-BII...