scholarly journals Lipopolysaccharide‐Binding Protein Increases Toll‐like Receptor 4–Dependent Activation by NontypeableHaemophilus influenzae

2001 ◽  
Vol 184 (7) ◽  
pp. 926-930 ◽  
Author(s):  
Irini Lazou Ahrén ◽  
Anders Bjartell ◽  
Arne Egesten ◽  
Kristian Riesbeck
Keyword(s):  
Binding Protein ◽  
Toll Like Receptor ◽  
Lipopolysaccharide Binding Protein ◽  
Toll Like Receptor 4 ◽  
Lipopolysaccharide Binding

Lipopolysaccharides in liver injury: molecular mechanisms of Kupffer cell activation

2002 ◽  
Vol 283 (2) ◽  
pp. G256-G265 ◽  
Author(s):  
Grace L. Su
Keyword(s):  
Liver Injury ◽  
Proinflammatory Cytokines ◽  
Kupffer Cells ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Binding Protein ◽  
Toll Like Receptor ◽  
Lipopolysaccharide Binding Protein ◽  
Toll Like Receptor 4 ◽  
Lipopolysaccharide Binding

Endogenous gut-derived bacterial lipopolysaccharides have been implicated as important cofactors in the pathogenesis of liver injury. However, the molecular mechanisms by which lipopolysaccharides exert their effect are not entirely clear. Recent studies have pointed to proinflammatory cytokines such as tumor necrosis factor-α as mediators of hepatocyte injury. Within the liver, Kupffer cells are major sources of proinflammatory cytokines that are produced in response to lipopolysaccharides. This review will focus on three important molecular components of the pathway by which lipopolysaccharides activate Kupffer cells: CD14, Toll-like receptor 4, and lipopolysaccharide binding protein. Within the liver, lipopolysaccharides bind to lipopolysaccharide binding protein, which then facilitates its transfer to membrane CD14 on the surface of Kupffer cells. Signaling of lipopolysaccharide through CD14 is mediated by the downstream receptor Toll-like receptor 4 and results in activation of Kupffer cells. The role played by these molecules in liver injury will be examined.

scholarly journals Aging-related liver degeneration is associated with increased bacterial endotoxin and lipopolysaccharide binding protein levels

2020 ◽  
Vol 318 (4) ◽  
pp. G736-G747
Author(s):  
Cheng Jun Jin ◽  
Anja Baumann ◽  
Annette Brandt ◽  
Anna Janina Engstler ◽  
Anika Nier ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Damage ◽  
Binding Protein ◽  
Bacterial Endotoxin ◽  
Toll Like Receptor ◽  
Hepatic Inflammation ◽  
Lipopolysaccharide Binding Protein ◽  
Toll Like Receptor 4 ◽  
Liver Degeneration ◽  
Lipopolysaccharide Binding

Aging is a risk factor in the development of many diseases, including liver-related diseases. The two aims of the present study were 1) to determine how aging affects liver health in mice in the absence of any interventions and 2) if degenerations observed in relation to blood endotoxin levels are critical in aging-associated liver degeneration. Endotoxin levels and markers of liver damage, mitochondrial dysfunction, insulin resistance, and apoptosis as well as the Toll-like receptor 4 (Tlr-4) signaling cascade were studied in liver tissue and blood, respectively, of 3- and 24-mo-old male C57BL/6J mice. In a second set of experiments, 3- to 4-mo-old and 14-mo-old female lipopolysaccharide-binding protein (LBP)−/− mice and littermates fed standard chow, markers of liver damage, insulin resistance, and mitochondrial dysfunction were assessed. Plasma activity of aspartate aminotransferase and histological signs of hepatic inflammation and fibrosis were significantly higher in old C57BL/6J mice than in young animals. The number of neutrophils, CD8α-positive cells, and mRNA expression of markers of apoptosis were also significantly higher in livers of old C57BL/6J mice compared with young animals, being also associated with a significant induction of hepatic Tlr-4 and LBP expression as well as higher endotoxin levels in peripheral blood. Compared with age-matched littermates, LBP−/− mice display less signs of senescence in liver. Taken together, our data suggest that, despite being fed standard chow, old mice developed liver inflammation and beginning fibrosis and that bacterial endotoxin may play a critical role herein. NEW & NOTEWORTHY Old age in mice is associated with marked signs of liver degeneration, hepatic inflammation, and fibrosis. Aging-associated liver degeneration is associated with elevated bacterial endotoxin levels and an induction of lipopolysaccharide-binding protein (LBP) and Toll-like receptor 4-dependent signaling cascades in liver tissue. Furthermore, in old aged LBP−/− mice, markers of senescence seem to be lessened, supporting the hypothesis that bacterial endotoxin levels might be critical in aging-associated decline of liver.

scholarly journals Kupffer cell activation by lipopolysaccharide in rats: Role for lipopolysaccharide binding protein and toll-like receptor 4

Hepatology ◽  
2000 ◽  
Vol 31 (4) ◽  
pp. 932-936 ◽  
Author(s):  
Grace L. Su ◽  
Richard D. Klein ◽  
Alireza Aminlari ◽  
Hong Y. Zhang ◽  
Lars Steinstraesser ◽  
...  
Keyword(s):  
Kupffer Cell ◽  
Cell Activation ◽  
Binding Protein ◽  
Toll Like Receptor ◽  
Lipopolysaccharide Binding Protein ◽  
Toll Like Receptor 4 ◽  
Lipopolysaccharide Binding

scholarly journals Estrogens Augment Cell Surface TLR4 Expression on Murine Macrophages and Regulate Sepsis Susceptibility in Vivo

Endocrinology ◽  
2009 ◽  
Vol 150 (8) ◽  
pp. 3877-3884 ◽  
Author(s):  
Jennifer A. Rettew ◽  
Yvette M. Huet ◽  
Ian Marriott
Keyword(s):  
Cell Surface ◽  
Immune Responses ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Toll Like Receptor ◽  
Lipopolysaccharide Binding Protein ◽  
Toll Like Receptor 4 ◽  
17Β Estradiol ◽  
Lipopolysaccharide Binding

Gender-based differences exist in infectious disease susceptibility. In general, females generate more robust and potentially protective humoral and cell-mediated immune responses after antigenic challenge than their male counterparts. Furthermore, evidence is accumulating that sex may also influence the early perception of microbial challenges and the generation of inflammatory immune responses such as sepsis. These differences have previously been attributed to the actions of reproductive hormones. Whereas androgens have been shown to suppress acute host immune responses to bacterial endotoxin challenge, estrogens have been found to promote increased resistance to bacterial infections. However, the mechanisms by which estrogens exert immunoprotective effects have not been established. In this study, we investigated the in vivo effects of 17β-estradiol on endotoxin susceptibility in mice. Importantly, we have examined the actions of this female reproductive hormone on the expression of pattern recognition receptors that recognize bacterial endotoxin by key innate immune sentinel cells. We show that removal of endogenous estrogens decreases both pro- and antiinflammatory cytokine production, with a concomitant reduction in circulating levels of lipopolysaccharide-binding protein and cell surface expression of Toll-like receptor 4 on murine macrophages. Exogenous in vivo replacement of 17β-estradiol, but not progesterone, significantly elevates sera lipopolysaccharide-binding protein levels and cell surface expression of Toll-like receptor 4 and CD14 on macrophages. Furthermore, this effect corresponds with significantly higher inflammatory cytokine levels after in vivo lipopolysaccharide challenge and a marked increase in endotoxin-associated morbidity. Taken together, these data provide a potential mechanism underlying the immunoenhancing effects of estrogens.

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