Innate immune reactivity of the ileum-liver axis in nonalcoholic steatohepatitis.

Background: Over-proliferation and bacterial translocation of Gram-negative bacilli within the intestinal flora, and increased portal venous levels of endotoxins, are involved in nonalcoholic steatohepatitis (NASH).

Aim: To evaluate the innate immune response in the small intestine and liver using the rat NASH model.

Methods: We produced the NASH model by administering a choline-deficient amino acid-defined diet to F344 rats.

Therapeutic effects of cytokine modulator Y-40138 in the rat alcoholic liver disease model.

Background And Aim: Inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ), induce liver injury in the rat alcoholic liver disease (ALD) model. Y-40138 is known to suppress the pro-inflammatory cytokines and augment the anti-inflammatory cytokines. We investigated whether or not Y-40138 may be effective as a novel immunotherapy in the rat ALD model.

Salvage effect of E5564, Toll-like receptor 4 antagonist on d-galactosamine and lipopolysaccharide-induced acute liver failure in rats.

Background And Aims: The transmembrane protein Toll-like receptor 4 (TLR4), which exists mainly in macrophages such as Kupffer cells of the liver, plays an important role in recognizing and mediating macrophage activation and pro-inflammatory cytokine release. Activation of the pro-inflammatory cytokine cascade, including tumor necrosis factor-alpha (TNF-alpha), has a pivotal role in the progression of severe liver injury. D-galactosamine (GalN) and lipopolysaccharide (LPS)-induced liver injury in rats is an experimental model of fulminant hepatic failure, where TNF-alpha plays a central role in the progression of liver injury.

Immunotherapy for nonalcoholic steatohepatitis using the multiple cytokine production modulator Y-40138.

Aim: To investigate the possible use of the multiple cytokine production modulator, Y-40138, as a novel immunotherapy in the rat nonalcoholic steatohepatitis (NASH) model.

Methods: We allocated 6-wk-old male F344 rats to choline-supplemented, L-amino acid-defined (CSAA) diet (control group), CSAA diet + Y-40138 (control + Y-40138 group), choline-deficient, L-amino acid-defined (CDAA) diet (NASH group), or CDAA diet + Y-40138 (NASH + Y-40138 group). In each group, we measured the plasma alanine aminotransferase (ALT) levels, and the plasma and liver levels of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-10 (IL-10).

Therapeutic approach to regulate innate immune response by Toll-like receptor 4 antagonist E5564 in rats with D-galactosamine-induced acute severe liver injury.

Background And Aims: Toll-like receptor 4 (TLR4) is a transmembrane protein, existing mainly in macrophages, such as Kupffer cells of the liver. It plays an important role in recognizing and mediating macrophage activation and pro-inflammatory cytokine release. Activation of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha is pivotal in the progression of liver injury.

Innate immune reactivity of the liver in rats fed a choline-deficient L-amino-acid-defined diet.

Aim: To investigate the innate immune reactivity of tumor necrosis factor-alpha (TNF-alpha), Toll-like receptor 4 (TLR4), and CD14 in the liver of non-alcoholic steatohepatitis (NASH) model rats.

Methods: Male F344 rats were fed a choline-deficient L-amino-acid-defined (CDAA) diet. The rats were killed after 4 or 8 wk of the diet, and their livers were removed for immunohistochemical investigation and RNA extraction.

Decreased phagocytic activity of Kupffer cells in a rat nonalcoholic steatohepatitis model.

Aim: To investigate Kupffer cell dynamics and phagocytic activity, using a rat nonalcoholic steatohepatitis (NASH) model.

Methods: Male F344 rats were fed either a control diet or a choline-deficient L-amino acid-defined (CDAA) diet, followed by contrast enhanced ultrasonography (CEUS) using Levovist. The uptake of latex beads by the Kupffer cells was determined by fluorescent microscopy.

Expression of Toll-like receptor 4 in various organs in rats with D-galactosamine-induced acute hepatic failure.

Background And Aims: Activation of the pro-inflammatory cytokine cascade, including tumor necrosis factor alpha (TNF-alpha) is considered to play an important role in the pathophysiology and clinical outcome of severe liver injury. Kupffer cells, resident macrophages of the liver, have a transmembrane protein Toll-like receptor 4 (TLR4), which recognizes endotoxin (lipopolysaccharide; LPS) or LPS-CD14 complex and mediates macrophage activation and pro-inflammatory cytokine release. D-Galactosamine (GalN), a hepatocyte-specific inhibitor of RNA synthesis, is known to sensitize animals to the lethal effects of LPS and TNF-alpha.

Effect of prostaglandin E receptor subtype EP4 selective agonist on the secretion of tumor necrosis factor-alpha by macrophages in acute ethanol-loaded rats.

Background: It is suggested that endotoxin and proinflammatory cytokines play an important role in the development and progression of alcoholic liver disease. Recently, a prostaglandin receptor subtype EP4 agonist with cytoprotective effect has been developed. We examined the efficacy of an EP4 agonist ONO-AE1-437 on tumor necrosis factor-alpha (TNF-alpha) secretion of Kupffer cells, splenic macrophages, and alveolar macrophages in acute ethanol-loaded rats.

The production of tumor necrosis factor-alpha by macrophages in rats with acute alcohol loading.

Background: It is suggested that endotoxin, proinflammatory cytokines, and lipopolysaccharide-binding protein (LBP) play an important role in the development of alcoholic liver disease. Our previous study showed that splenic macrophages were important for endotoxin uptake and excessive production of tumor necrosis factor (TNF) in rats given large amounts of alcohol. To study the pathophysiological roles of macrophages in alcoholic liver diseases, we examined the production of TNF-alpha by rat Kupffer cells, splenic macrophages, and alveolar macrophages with acute alcohol loading in the presence or absence of LBP.

Effect of alcohol on the secretion of tumor necrosis factor-alpha by macrophages in the presence of rat serum.

Background: It is suggested that endotoxin, proinflammatory cytokines, and lipopolysaccharide-binding protein (LBP) play an important role in the development of alcoholic liver disease. Our previous study showed that splenic macrophages were important for endotoxin uptake and excessive production of tumor necrosis factor (TNF) in rats given large amounts of alcohol. To determine the pathophysiological roles of macrophages in alcoholic liver disease, we examined the effect of ethanol on TNF-alpha secretion of rat Kupffer cells, alveolar macrophages, and peritoneal macrophages in the presence or absence of LBP.