Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Language
Publication year range
1.
J Nat Prod ; 81(6): 1435-1443, 2018 06 22.
Article in English | MEDLINE | ID: mdl-29851490

ABSTRACT

Sepsis is a systemic inflammatory response to pathogenic infection that currently has no specific pharmaceutical interventions. Instead, antibiotics administration is considered the best available option, despite increasing drug resistance. Alternative strategies are therefore urgently required to prevent sepsis and strengthen the host immune system. One such option is tamarixetin (4'- O-methylquercetin), a naturally occurring flavonoid derivative of quercetin that protects against inflammation. The purpose of this study was to determine whether the anti-inflammatory effects of tamarixetin protect against the specific inflammatory conditions induced in lipopolysaccharide (LPS) or Escherichia coli K1 models of sepsis. Our study showed that tamarixetin reduced the secretion of various inflammatory cytokines by dendritic cells after activation with LPS. It also promoted the secretion of the anti-inflammatory cytokine interleukin (IL)-10 and specifically increased the population of IL-10-secreting immune cells in LPS-activated splenocytes. Tamarixetin showed general anti-inflammatory effects in mouse models of bacterial sepsis and decreased bacteria abundance and endotoxin levels. We therefore conclude that tamarixetin has superior anti-inflammatory properties than quercetin during bacterial sepsis. This effect is associated with an increased population of IL-10-secreting immune cells and suggests that tamarixetin could serve as a specific pharmaceutical option to prevent bacterial sepsis.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Disaccharides/pharmacology , Interleukin-10/metabolism , Quercetin/analogs & derivatives , Sepsis/drug therapy , Animals , Cytokines/metabolism , Dendritic Cells/drug effects , Escherichia coli/pathogenicity , Female , Inflammation/drug therapy , Inflammation/metabolism , Lipopolysaccharides/pharmacology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Quercetin/pharmacology , Sepsis/metabolism
2.
Biochem Biophys Res Commun ; 486(4): 998-1004, 2017 May 13.
Article in English | MEDLINE | ID: mdl-28363868

ABSTRACT

Analysis of the signaling mechanism triggered by endotoxin-mediated toll-like receptor-4 activation using immune cell systems or rodent models may help identify potential agents for the prevention of Gram-negative bacteria infection. ß-agarase cleaves the ß-1,4-linkages of agar to produce neoagarooligosaccharides (NAOs), which have various physiological functions. The aim of this study was to investigate the efficacy of NAOs in preventing experimental sepsis caused by the administration of endotoxin or Gram-negative bacteria. Organ damage and neutrophil infiltration in an endotoxemia and septic-shock mouse model were suppressed by NAOs. Pro-inflammatory cytokine level was decreased, but IL-10 level was increased by NAO-treatment. Further induction by NAOs in the presence of endotoxin was associated with a significant induction of A20 and cyclooxygenase (COX)-2 expressions. Our data suggest that NAOs have a beneficial preventive effect in septic shock correlated with the enhancement of IL-10 via the induction of A20 and COX-2.


Subject(s)
Cyclooxygenase 2/immunology , Interleukin-10/immunology , Oligosaccharides/administration & dosage , Shock, Septic/immunology , Shock, Septic/prevention & control , Tumor Necrosis Factor alpha-Induced Protein 3/immunology , Agar/chemistry , Animals , Dose-Response Relationship, Drug , Female , Mice , Mice, Inbred C57BL , Oligosaccharides/chemistry , Treatment Outcome
3.
BMB Rep ; 49(10): 554-559, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27439605

ABSTRACT

Mycobacterium abscessus, a member of the group of non-tuberculous mycobacteria, has been identified as an emerging pulmonary pathogen in humans. However, little is known about the protective immune response of antigenpresenting cells, such as dendritic cells (DCs), which guard against M. abscessus infection. The M. abscessus gene MAB1843 encodes D-alanyl-D-alanine dipeptidase, which catalyzes the hydrolysis of D-alanyl-D-alanine dipeptide. We investigated whether MAB1843 is able to interact with DCs to enhance the effectiveness of the host's immune response. MAB1843 was found to induce DC maturation via toll-like receptor 4 and its downstream signaling pathways, such as the mitogen-activated protein kinase and nuclear factor kappa B pathways. In addition, MAB1843-treated DCs stimulated the proliferation of T cells and promoted Th1 polarization. Our results indicate that MAB1843 could potentially regulate the immune response to M. abscessus, making it important in the development of an effective vaccine against this mycobacterium. [BMB Reports 2016; 49(10): 554-559].


Subject(s)
Bacterial Proteins/metabolism , Dendritic Cells/metabolism , Dipeptidases/metabolism , Mycobacterium/enzymology , Th1 Cells/immunology , Animals , Bacterial Proteins/genetics , Cell Polarity/drug effects , Cell Proliferation/drug effects , Cytokines/analysis , Dendritic Cells/cytology , Dendritic Cells/drug effects , Dipeptidases/genetics , Dipeptides/chemistry , Endocytosis , Lipopolysaccharides/metabolism , Lipopolysaccharides/toxicity , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Mitogen-Activated Protein Kinases/metabolism , Mycobacterium/genetics , Mycobacterium/physiology , NF-kappa B/metabolism , Recombinant Proteins/biosynthesis , Recombinant Proteins/isolation & purification , Recombinant Proteins/pharmacology , Th1 Cells/cytology , Th1 Cells/metabolism , Toll-Like Receptor 4/deficiency , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...