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Regulation of macrophage activation in the liver after acute injury: Role of the fibrinolytic system.

The liver functions, in part, to prevent exposure of the body to potentially harmful substances ingested in the diet. While it is highly efficient at accomplishing this, it is frequently prone to liver injury due to the biotransformation of xenobiotics into toxic metabolites. To counter this injury, the liver has evolved a unique capacity to rapidly and efficiently repair itself. Successful resolution of acute liver injury relies on hepatic macrophage populations that orchestrate the reparative response. After injury, Kupffer cells, the resident macrophages of the liver, become activated and s…

Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) and its complications are an expanding health problem associated with the metabolic syndrome. Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells localized at the interface between the blood derived from the gut and the adipose tissue on the one side, and other liver cells on the other side. In physiological conditions, LSECs are gatekeepers of liver homeostasis. LSECs display anti-inflammatory and anti-fibrogenic properties by preventing Kupffer cell and hepatic stellate cell activation and regulating intrahepatic vascu

Notch signaling affects biliary fibrosis via transcriptional regulation of RBP-jκ in an animal model of chronic liver disease.

Liver repair in patients with a chronic liver disease requires the orchestrated action of epithelial, mesenchymal, and inflammatory cells. N … o unveil how ductular cells interact with other liver cell types, such as hepatic stellate cells or Kupffer cells,in patients with cholestatic liver diseases based on Notch signaling. These results suggest that controlling the ductular reaction using a synthetic ring type decoy RBP-jκ ODN will help develop a novel therapeutic approach targeting biliary fibrosis …

Pathologic highlights of dengue hemorrhagic fever in 13 autopsy cases from Myanmar.

Vascular permeability, thrombocytopenia, liver pathology, complement activation, and altered hemostasis accompanying a febrile disease are t … l antigens (E, NS1, and nonsecreting NS3). In the liver, DENV infection occurred in hepatocytes and Kupffer cells but not in endothelial cells. Liver damage was associated with deposition on hepatocytes of complement components of both classical and alternative pathways. Evidence of dengue viral replication was observed in macrophage-like cells in spleens and l …

Bile duct changes in alcoholic liver disease. The Veterans Administration Cooperative Study Group.

The histologic significance of various changes in the bile ductal structures as observed by cytokeratin immunoperoxidase assay was studied in 122 patients with alcoholic liver disease (ALD) as a part of a large Veterans Administration Cooperative Study on alcoholic hepatitis. Four types of morphologic changes in the biliary structures were observed: 1) proliferation of interlobular bile ducts in the portal tracts; 2) marginal bile ductular proliferation at the periphery of the portal tracts; 3) appearance of bile duct type cells ("oval cells") in the liver parenchyma; and 4) metaplasia of bile

Expression of insulin-like growth factor-I and insulin-like growth factor binding proteins during thioacetamide-induced liver cirrhosis in rats.

OBJECTIVE: The liver plays a central role in insulin-like growth factor (IGF) homeostasis providing the majority of circulating IGF-I and so … interface in the cirrhotic nodule that correlated with reduced IGFBP-3 mRNA expression observed in Kupffer cells (KC) and sinusoidal endothelial cells (SEC) isolated from macronodular cirrhotic livers. CONCLUSION: Cirrhosis is accompanied by an altered spatial expression of IGFBP-3 in liver tissue, which is characterized by decreased levels of IGFBP-3 mRNA in …

Targeted inhibition of pathobiont virulence factor mitigates alcohol-associated liver disease.

Alcohol-associated liver disease poses a global health burden with high mortality. Imbalances in the gut microbiota are important for diseas … urface. This enables kpsM-positive E. coli to evade phagocytosis by the scavenger receptor Marco on Kupffer cells in the liver, leading to bacterial spread. Importantly, inhibiting kpsM-dependent capsules with the small molecule 2-(4-phenylphenyl)benzo[g]quinoline-4-carboxylic acid (C7) attenuated ethanol-induced liver disease in mice. We show that precision ta …

TRIF and IRF-3 binding to the TNF promoter results in macrophage TNF dysregulation and steatosis induced by chronic ethanol.

Chronic ethanol (EtOH) abuse results in the development of steatosis, alcoholic hepatitis, and cirrhosis. Augmented TNF-alpha production by macrophages and Kupffer cells and signaling via the p55 TNF receptor have been shown to be critical for these effects of chronic EtOH; however, the molecular mechanisms leading to augmented TNF-alpha production remain unclear. Using cell culture models and in vivo studies we demonstrate that chronic EtOH results in increased TNF-alpha transcription, which is independent of NF-kappaB. Using reporter assays and chromatin immunoprecipitation we found that thi…

Studies on folk medicine "thang-kau-tin" from Taiwan. (I). The anti-inflammatory and liver-protective effect.

Five species of crude drugs are used as "Thang-kau-tin" on Taiwan market: (1) the stem of Mallotus repandus (Willd.) Muell.-Arg, (2) the ste … ein including fatty change, ballooning degeneration, cell necrosis, the increase in lymphocytes and Kupffer cells were improved by the treatment with the group of crude drugs as mentioned above.

The mechanism of organ injury in alcoholics: implications for therapy.

Organ damage due to alcohol abuse includes especially the CNS and the GI tract. The mechanism of liver injury has been studied in depth. Alterations in membrane fluidity, signal transduction, cytochrome, P-450 induction, oxidative stress, acetaldehyde adducts, eicosanoid metabolism, cytoskeletal function, energy metabolism, O2 consumption, microcirculation, Kupffer cell and ito cell activation, immune injury, and gene expression have been documented. Therapeutic implications of these studies include oxandrolone, PTU and colchicine. Pancreatic injury has been studied in vivo and with isolated a

A glycogen storage disease in rats. Morphological and biochemical investigations.

Liver and heart from a substrain of the NZR/Gd rat in which there is an inherited deficiency of liver phosphorylase b kinase was examined by … hepatocytes. Free glycogen was present in the space of Disse and sinusoids and within lysosomes in Kupffer cells. There were increased amounts of collagen in the space of Disse. The changes resemble those described in human glycogen storage disease IXa. A study of hepatic tissue from fasted rats showed that affected animals have an impaired ability to mobilise …

MyD88 Inhibition Ameliorates Diabetes-Induced Hepatic Inflammation and Gluconeogenesis Through Adipose IL-10 Induction.

Myeloid differentiation factor 88 (MyD88) signaling plays a central role in inflammatory pathway activation. Adipose-derived interleukin-10 (IL-10), which is induced by insulin and lipopolysaccharides, suppresses hepatic glucose production. This study investigated the role of MyD88/IL-10 signaling in diabetes-induced systemic inflammation and hepatic gluconeogenesis. Stromal vascular fractions (SVFs) were isolated from the adipose tissue of Leprdb/db and Leprdb/dbMyD88-/- mice and treated with IL-10 followed by analysis of inflammatory cytokine expression. IL-10 (10 or 50 ng) was injected into

The nicotinamide adenine dinucleotide phosphate oxidase (NOX) homologues NOX1 and NOX2/gp91(phox) mediate hepatic fibrosis in mice.

UNLABELLED: Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is a multicomponent enzyme that mediates electron transfer from nicoti … liver cells, including hepatic stellate cells (HSCs), and bone marrow (BM)-derived cells, including Kupffer cells (KCs), to hepatic reactive oxygen species (ROS) generation and hepatic fibrosis was assessed in vitro and in vivo using NOX1 or NOX2 BM chimeric mice. Hepatic NOX1 and NOX2 messenger RNA expression was increased in the two experimental mouse models …

Mechanisms and pathophysiological significance of sterile inflammation during acetaminophen hepatotoxicity.

Acetaminophen (APAP) is a widely used analgesic drug, which can cause severe liver injury after an overdose. The intracellular signaling mec … ture on the role of various DAMPs, cytokines and chemokines, and the pathophysiological function of Kupffer cells, neutrophils, monocytes and monocyte-derived macrophages, and NK and NKT cells during APAP hepatotoxicity. Careful evaluation of results and experimental designs of studies dealing with the inflammatory response after APAP toxicity provide very limi …

Emx2 is an essential regulator of ciliated cell development across embryonic tissues.

Cilia are hair-like organelles with vital physiological roles, and ciliogenesis defects underlie a range of severe congenital malformations and human diseases. Here, we report that empty spiracles homeobox 2 (emx2) is essential for cilia development across multiple embryonic tissues including the ear, neuromasts and Kupffer's vesicle (KV), which establishes left/right axial pattern. emx2 deficient embryos manifest altered fluid homeostasis and kidney defects including decreased multiciliated cells (MCCs), determining that emx2 is essential to properly establish several renal lineages. Further,

Endotoxin-inducible cytotoxicity in liver cell cultures--I.

It is known that rodents challenged with a combination of galactosamine and endotoxin develop a fulminant hepatitis within several hours. Until now, no in-vitro correlate for this organ-specific lesion has been described. Here, in-vitro conditions have been developed which allow examination of lipopolysaccharide (endotoxin)-inducible cell injury to hepatocytes. Under these in-vitro conditions (RPMI 1640 supplemented with 10% calf serum, 40% oxygen tension) which require the presence of functionally intact Kupffer cells, a concentration-dependent lactate dehydrogenase release is inducible by di…

Longitudinal multiomics profiling of extracorporeal cross-circulation with pig liver xenografts in human decedents.

Extracorporeal liver cross-circulation (ELC) using gene-edited porcine liver xenografts offers a potential bridge therapy for liver failure. We previously performed five ELC procedures in four brain-dead human decedents, during which the recipients developed severe thrombocytopenia. The porcine liver xenografts maintained their parenchymal structure, with immune cell infiltration and detectable IgM deposition on endothelial cells. Here, to investigate the underlying host-xenograft interactions, we performed longitudinal proteomic, lipidomic and metabolomic profiling of 64 blood samples, alongs

Геномические и стеноскопические особенности интеграции ВИЧ-инфекции в лечебно-наивных, ВИЧ-позитивных детей с хроническим ВИЧ-инфекцией.

Интеграция вируса В (ГБВ) представляет собой серьезное препятствие для лечения ГБВ; однако ландшафт интеграции ГБВ и местной иммунной реакции на трансформационно активную вирусную интеграцию у детей с хронической ГБВ остается неясным. В этой связи мы стремились прояснить этот ландшафт в этой популяции. МЕТОДЫ: Геномический анализ с использованием стратегии улавливания на основе зондов был проведен в отношении 18 детей и 28 взрослых, страдающих хроническим ВИЧ-инфекцией. Пространственная транскриптомика (ST) была произведена на 12 детей из нашей группы и на 3 взрослых из публичной базы данных.

Совпадение в аннотации оригинала
BACKGROUND: Hepatitis B virus (HBV) integration represents a major obstacle to curing HBV; however, the landscape of HBV integration and loc … reduced adaptive immune cells (e.g., CD8+ T cells) but increased innate components (myeloid cells, Kupffer cells, activated dendritic cells) and APC co-stimulation, whereas adults exhibited a uniform reduction of immune cell populations. INTERPRETATION: Compared with adults, children exhibit lower clonal expansion of HBV-integrated hepatocytes and distinct im …

Immunomodulatory Therapy of Inflammatory Liver Disease Using Selectin-Binding Glycopolymers.

Immunotherapies have the potential to significantly advance treatment of inflammatory disease and cancer, which are in large part driven by … ausing hepatotoxicity. The glycosylated binder most potently targeted resident hepatic macrophages (Kupffer cells) and protected mice from acute toxic liver injury in the two different experimental models, carbon tetrachloride (CCl4) or Concanavalin A (ConA)-based hepatitis. Its sulfated counterpart, on the other hand, induced a decrease in infiltrating and res …

Elimination of porcine hemopoietic cells by macrophages in mice.

The difficulty in achieving donor hemopoietic engraftment across highly disparate xenogeneic species barriers poses a major obstacle to expl … cells in vivo. Because injection of M-liposomes i.v. mainly depletes splenic macrophages and liver Kupffer cells, the spleen and/or liver are likely the primary sites of porcine cell clearance in vivo.