Retinoid receptors are members of nuclear receptor superfamily consisting of two distinct families: RARs (retinoic acid receptors) and RXRs (retinoid X receptors). Each family contains three receptor subtypes α, β, and γ. Retinoids transduce their effects through binding to retinoid receptors and inhibit transcription factors such as activator protein-1 and nuclear factor-κB (NF-κB) both of which regulate the transcription of several inflammatory genes.
View Article and Find Full Text PDFObjectives: P128 is a recombinant chimeric ectolysin with potent antistaphylococcal activity. P128 was evaluated as monotherapy and in combination with two standard-of-care (SoC) antibiotics, vancomycin and daptomycin, in mouse models of Staphylococcus aureus bacteraemia.
Methods: Healthy BALB/c mice were challenged (intraperitoneally) with 109 cfu of MRSA strain COL or USA300 and treated with a single dose of P128 (0.
Purpose: P128, a phage-derived lysin, exerts antibacterial activity on staphylococci by cleaving the pentaglycine-bridge of peptidoglycan. We sought to determine whether the presence of P128 could re-sensitize drug-resistant bacteria to antibiotics by virtue of its cell wall degrading property.
Methodology: P128 was tested in combination with standard-of-care (SoC) drugs by chequerboard assays on planktonic cells and biofilms of strains individually resistant to these drugs.
Bacterial biofilms are highly resistant to the action of antibiotics. Presence of persisters, phenotypically resistant populations of bacterial cells, is thought to contribute toward recalcitrance of biofilms. The phage-derived lysins, by virtue of their ability to cleave the peptidoglycan of bacterial cells in an enzymatic manner, have the unique ability to kill dormant cells.
View Article and Find Full Text PDFcauses systemic infections with high morbidity and mortality, and the emergence of drug-resistant strains is a rapidly growing clinical concern. Novel therapeutic agents are required to tackle infections. P128 is a bacteriophage-derived chimeric ectolysin with potent and rapid bactericidal activity against In the present study, the efficacy of P128 was evaluated in a newly developed rat model of bacteremia.
View Article and Find Full Text PDFBackground: Exposure to animal barn air is an occupational hazard that causes lung dysfunction in barn workers. Respiratory symptoms experienced by workers are typically associated with endotoxin and TLR4 signalling, but within these environments gram negative bacteria constitute only a portion of the total microbial population. In contrast, unmethylated DNA can be found in all bacteria, some viruses, and mold.
View Article and Find Full Text PDFAm J Physiol Lung Cell Mol Physiol
November 2015
The mechanisms of excessive migration of activated neutrophils into inflamed lungs, credited with tissue damage, are not fully understood. We explored the hitherto unknown expression of leukocyte-specific protein 1 (LSP1) in human and mouse lungs and neutrophils and examined its role in neutrophil migration in acute lung inflammation. Autopsied septic human lungs showed increased LSP1 labeling in epithelium, endothelium, and leukocytes, including in their nuclei compared with normal lungs.
View Article and Find Full Text PDFRetinoids play an important role in lung development and immune response. The effects of retinoids are mediated through 2 families of retinoid receptors: retinoic acid receptors (RARs) and retinoid X receptors (RXRs), with alpha (α), beta (β), and gamma (γ) subtypes in each family. To date, no data exist on the expression pattern of retinoid receptors in lungs of cattle, dogs, and pigs.
View Article and Find Full Text PDFVet Immunol Immunopathol
February 2014
Activated neutrophils live longer, produce toxic metabolites and cause considerable tissue injury, which is central to the pathogenesis of many inflammatory conditions. Retinoids are a class of lipophilic compounds with anti-inflammatory effects. We examined the effect of retinoic acid on apoptosis in normal and activated neutrophils.
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