A5037459119- Immune Response and Inflammation
- Antimicrobial Peptides and Activities
- Invertebrate Immune Response Mechanisms
- Glycosylation and Glycoproteins Research
- Aquaculture disease management and microbiota
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Bacterial Genetics and Biotechnology
- Gut microbiota and health
- Pediatric health and respiratory diseases
- Escherichia coli research studies
- Vibrio bacteria research studies
- NF-κB Signaling Pathways
- Asthma and respiratory diseases
- Antimicrobial Resistance in Staphylococcus
- Antibiotic Resistance in Bacteria
- T-cell and B-cell Immunology
- Carbohydrate Chemistry and Synthesis
- Proteoglycans and glycosaminoglycans research
- Adipokines, Inflammation, and Metabolic Diseases
- Cell Adhesion Molecules Research
- Viral gastroenteritis research and epidemiology
- Immune cells in cancer
- Probiotics and Fermented Foods
Indiana University Northwest
2010-2021
Indiana University School of Medicine
2009-2021
Indiana University
1992-2012
University School
2002-2003
Lexicon Pharmaceuticals (United States)
2003
Stockholm University
2003
University of Louisville
2002
Bipar
1980-1999
Research Center Borstel - Leibniz Lung Center
1994-1997
Temple College
1978-1985
The life-threatening complications of sepsis in humans are elicited by infection with Gram-negative as well Gram-positive bacteria. Recently, lipopolysaccharide (LPS), a major biologically active agent bacteria, was shown to mediate cellular activation member the human Toll-like receptor family, (TLR) 2. Here we investigate mechanism soluble peptidoglycan (sPGN) and lipoteichoic acid (LTA), main stimulatory components Like LPS, sPGN LTA bind glycosylphosphatidylinositol-anchored membrane...
Abstract Invasive infection with Gram-positive and Gram-negative bacteria often results in septic shock death. The basis for the earliest steps innate immune response to bacterial is poorly understood. LPS component of cell wall appears activate cells via CD14 Toll-like receptor (TLR) 2 TLR4. We hypothesized that might also be recognized by TLRs. Heterologous expression human TLR2, but not TLR4, fibroblasts conferred responsiveness Staphylococcus aureus Streptococcus pneumoniae as evidenced...
The innate immune system recognizes microorganisms through a series of pattern recognition receptors that are highly conserved in evolution. Insects have family 12 peptidoglycan proteins (PGRPs) recognize peptidoglycan, ubiquitous component bacterial cell walls. We report cloning three novel human PGRPs (PGRP-L, PGRP-Iα, and PGRP-Iβ) together with the previously cloned PGRP-S, define new molecules. PGRP-L, PGRP-Iβ 576, 341, 373 amino acids coded by five, seven, eight exons on chromosomes 19...
Dysbiosis is a hallmark of inflammatory bowel disease (IBD), but it unclear which specific intestinal bacteria predispose to and protect from IBD how they are regulated. Peptidoglycan recognition proteins (Pglyrps) antibacterial, participate in maintaining microflora, modulate responses. Mice deficient any one the four Pglyrp genes more sensitive dextran sulfate sodium (DSS)-induced colitis, stools Pglyrp-deficient mice transferred wild type (WT) germ-free them much severe colitis than WT...
Abstract Dendritic cells (DCs) are capable of cross-presenting exogenous Ag to CD8+ CTLs. Detection microbial products by Toll-like receptors (TLRs) leads activation DCs and subsequent orchestration an adaptive immune response. We hypothesized that TLR ligands could activate cross-present Using CTLs in vitro cross-presentation system, we show a subset ligands, namely TLR3 (poly(inosinic-cytidylic) acid) TLR9 (immunostimulatory CpG DNA), induces cross-presentation. In contrast presentation...
The hypothesis that soluble peptidoglycan (sPGN, a macrophage-activator from Gram-positive bacteria) binds to CD14 (a lipopolysaccharide (LPS) receptor) was tested. sPGN specifically bound in the following three assays: binding of 32P-CD14 (sCD14) agarose-immobilized sPGN, enzyme-linked immunosorbent assay, and photoaffinity cross-linking. sCD14 also muramyl dipeptide or GlcNAc-muramyl but not PGN pentapeptide. Binding both ReLPS (where is LPS Salmonella minnesota Re 595) competitively...
Peptidoglycan recognition proteins (PGRPs) are pattern molecules coded by up to 13 genes in insects and 4 mammals. In PGRPs activate antimicrobial pathways the hemolymph cells, or peptidoglycan (PGN)-lytic amidases. mammals one PGRP is an antibacterial neutrophil protein. We report that human PGRP-L a Zn2+-dependent N-acetylmuramoyl-l-alanine amidase (EC 3.5.1.28), enzyme hydrolyzes amide bond between MurNAc l-Ala of bacterial PGN. The minimum PGN fragment hydrolyzed MurNAc-tripeptide. has...
Skin and mucous membranes come in contact with external environment protect tissues from infections by producing antimicrobial peptides. We report that human peptidoglycan recognition proteins 3 4 (PGLYRP3 PGLYRP4) are secreted as 89-115-kDa disulfide-linked homo- heterodimers bactericidal against several pathogenic nonpathogenic transient, but not normal flora, Gram-positive bacteria. PGLYRP3 PGLYRP4 also bacteriostatic toward all other tested bacteria, which include Gram-negative bacteria...
Since the ability of peptidoglycan (PGN) to activate Toll-like receptor 2 (TLR2) was recently questioned, we reevaluated activation TLR2 by PGN. Polymeric soluble or insoluble Staphylococcus aureus PGN, repurified sodium dodecyl sulfate phenol extraction, activated at 0.1 1 10 mug/ml, respectively, and induced tumor necrosis factor alpha production. The but not lipoteichoic acid, abolished muramidase digestion. We conclude that polymeric S. PGN is a activator.
Abstract MD-2 is associated with Toll-like receptor 4 (TLR4) on the cell surface and enables TLR4 to respond LPS. We tested whether enhances or responses of both TLR2 Gram-negative Gram-positive bacteria their components. without did not efficiently highly purified LPS partial structures. enabled nonactivating protein-free LPS, mutants, lipid A enhanced TLR2-mediated peptidoglycan, lipoteichoic acid a wide variety structures, bacteria, acid, but lipopeptide. physically TLR2, this association...
Peptidoglycan recognition protein (PGRP) is conserved from insects to mammals. In insects, PGRP recognizes bacterial cell wall peptidoglycan (PGN) and activates prophenoloxidase cascade, a part of the insect antimicrobial defense system. Because mammals do not have its function in unknown. However, it was suggested that an identical (Tag7) tumor necrosis factor-like cytokine. Therefore, aim this study identify Mouse bound PGN with fast kinetics nanomolar affinity (<i>K</i> <sub>d</sub> = 13...
We have investigated the interaction of soluble peptidoglycan (sPG), in comparison with lipopolysaccharide (LPS), human mononuclear cells (MNC) by determining capacity sPG to induce interleukin-6 (IL-6) and IL-1 release. In addition, we modulation their anti-CD14 monoclonal antibody partial structures LPS. found that sPG, like LPS, was able IL-6 production MNC. However, dose-response experiments revealed at least 3,000 ng per ml necessary for induction, whereas optimal LPS concentration 1...
ABSTRACT This study was done to elucidate the signal transduction pathway of interleukin-8 (IL-8) induction by gram-positive bacteria. Bacteria (micrococci) and peptidoglycan (PGN) induced transcription IL-8 in HEK293 cells expressing Toll-like receptor 2 (TLR2) CD14 but not those TLR1 or TLR4. A mutation within NF-κB site promoter abrogated transcriptional two stimulants. Dominant negative myeloid differentiation protein (MyD88), IL-1 receptor-associated kinase (IRAK), NFκB-inducing (NIK),...