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Host Defense Proteins and Peptides with Lipopolysaccharide-Binding Activity from Marine Invertebrates and Their Therapeutic Potential in Gram-Negative Sepsis.
Mar Drugs
November 2023
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok 690022, Russia.
Sepsis is a life-threatening complication of an infectious process that results from the excessive and uncontrolled activation of the host's pro-inflammatory immune response to a pathogen. Lipopolysaccharide (LPS), also known as endotoxin, which is a major component of Gram-negative bacteria's outer membrane, plays a key role in the development of Gram-negative sepsis and septic shock in humans. To date, no specific and effective drug against sepsis has been developed.
View Article and Find Full Text PDFDisaccharide-Based Anionic Amphiphiles as Potent Inhibitors of Lipopolysaccharide-Induced Inflammation.
ChemMedChem
November 2018
Department of Chemistry, University of Natural Resources and Life Sciences, Muthgasse 18, 1190, Vienna, Austria.
Despite significant advances made in the last decade in the understanding of molecular mechanisms of sepsis and in the development of clinically relevant therapies, sepsis remains the leading cause of mortality in intensive care units with increasing incidence worldwide. Toll-like receptor 4 (TLR4)-a transmembrane pattern-recognition receptor responsible for propagating the immediate immune response to Gram-negative bacterial infection-plays a central role in the pathogenesis of sepsis and chronic inflammation-related disorders. TLR4 is complexed with the lipopolysaccharide (LPS)-sensing protein myeloid differentiation-2 (MD-2) which represents a preferred target for establishing new anti-inflammatory treatment strategies.
View Article and Find Full Text PDFAnti-endotoxic activity and structural basis for human MD-2·TLR4 antagonism of tetraacylated lipid A mimetics based on βGlcN(1↔1)αGlcN scaffold.
Innate Immun
July 2015
Department of Chemistry, University of Natural Resources and Life Sciences, Vienna, Austria
Interfering with LPS binding by the co-receptor protein myeloid differentiation factor 2 (MD-2) represents a useful approach for down-regulation of MD-2·TLR4-mediated innate immune signaling, which is implicated in the pathogenesis of a variety of human diseases, including sepsis syndrome. The antagonistic activity of a series of novel synthetic tetraacylated bis-phosphorylated glycolipids based on the βGlcN(1↔1)αGlcN scaffold was assessed in human monocytic macrophage-like cell line THP-1, dendritic cells and human epithelial cells. Two compounds were shown to inhibit efficiently the LPS-induced inflammatory signaling by down-regulation of the expression of TNF-α, IL-6, IL-8, IL-10 and IL-12 to background levels.
View Article and Find Full Text PDFGalleria mellonella native and analogue peptides Gm1 and ΔGm1. II) anti-bacterial and anti-endotoxic effects.
Biochim Biophys Acta
October 2014
Forschungszentrum Borstel, Division of Biophysics, Parkallee 10, 23845 Borstel, Germany. Electronic address:
Antimicrobial peptides (AMPs) are important components of the innate immune system of animals, plants, fungi and bacteria and are recently under discussion as promising alternatives to conventional antibiotics. We have investigated two cecropin-like synthetic peptides, Gm1, which corresponds to the natural overall uncharged Galleria mellonella native peptide and ΔGm1, a modified overall positively charged Gm1 variant. We have analysed these peptides for their potential to inhibit the endotoxin-induced secretion of tumour necrosis factor-α (TNF-α) from human mononuclear cells.
View Article and Find Full Text PDFInnate immune cocktail partially protects broilers against cellulitis and septicemia.
Avian Dis
December 2012
Vaccine and Infectious Disease Organization (VIDO), International Vaccine Centre (Intervac), University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK, Canada, S7N 5E3.
Antimicrobial/host defense peptides (A/HDP) are natural compounds that are found in leucocyte cells and on the skin and bodily fluids of birds, reptiles, and mammals. Not only do they possess antibacterial, antiviral, and antiparasitic characteristics but they also stimulate the host immune system to combat infectious diseases and may play a role in the promotion of wound repair. Gamma-amino butyric acid (GABA) is an amino acid-based inhibitory neurotransmitter in the brain that has also been shown to promote wound healing on skin.
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