NF-κB activation in Kupffer cells after partial hepatectomy

Yang, Liu; Magness, Scott T.; Bataller, Ramón; Rippe, Richard A.; Brenner, David A.

doi:10.1152/ajpgi.00526.2004

Cited by 51 publications

(47 citation statements)

References 31 publications

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“…Recent studies demonstrate an impairment of liver regeneration after depletion of KC which are the main source of CO within the liver [1,2,78]. This is as reflected by the downregulation of transcription factors like NFκB [1,49,131], the alteration of cytokine expression, and finally the decrease of hepatocellular proliferation. Moreover, KCs have been repeatedly associated with the intrahepatic control of microvascular blood flow in particular due to their potential to express vasoactive enzyme systems (Fig.…”

Section: No Co and H 2 Smentioning

confidence: 99%

A critical appraisal of the hemodynamic signal driving liver regeneration

Abshagen

Eipel

Vollmar

2012

Langenbecks Arch Surg

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Section: No Co and H 2 Smentioning

confidence: 99%

A critical appraisal of the hemodynamic signal driving liver regeneration

Abshagen

Eipel

Vollmar

2012

Langenbecks Arch Surg

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“…NF-B activity in HSCs was measured as previously described (39). Briefly, HSCs were transfected with a recombinant adenovirus vector containing a luciferase reporter gene driven by NF-B transcriptional activation (Ad5NF-BLuc, multiplicity of infection 500) for 12 h. Medium was replaced and cells were incubated with the compounds for 24 h. NF-B-mediated transcriptional induction was assessed with the Luciferase Assay System (BD Pharmigen).…”

Section: Experimental Animals and Study Design Thirty Apoementioning

confidence: 99%

Increased susceptibility to exacerbated liver injury in hypercholesterolemic ApoE-deficient mice: potential involvement of oxysterols

Ferré¹,

Martínez-Clemente²,

López-Parra³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Clària J. Increased susceptibility to exacerbated liver injury in hypercholesterolemic ApoEdeficient mice: potential involvement of oxysterols. Am J Physiol Gastrointest Liver Physiol 296: G553-G562, 2009. First published January 8, 2009 doi:10.1152/ajpgi.00547.2007.-The contribution of metabolic factors to the severity of liver disease is not completely understood. In this study, apolipoprotein E-deficient (ApoE Ϫ/Ϫ ) mice were evaluated to define potential effects of hypercholesterolemia on the severity of carbon tetrachloride (CCl 4)-induced liver injury. Under baseline conditions, hypercholesterolemic ApoE Ϫ/Ϫ mice showed increased hepatic oxidative stress (SOD activity/4-hydroxy-2-nonenal immunostaining) and higher hepatic TGF-␤1, MCP-1, and TIMP-1 expression than wild-type control mice. After CCl4 challenge, ApoE Ϫ/Ϫ mice exhibited exacerbated steatosis (Oil Red O staining), necroinflammation (hematoxylin-eosin staining), macrophage infiltration (F4/80 immunohistochemistry), and fibrosis (Sirius red staining and ␣-smooth muscle actin immunohistochemistry) and more severe liver injury [alanine aminotransferase (ALT) and aspartate aminotransferase] than wild-type controls. Direct correlations were identified between serum cholesterol and hepatic steatosis, fibrosis, and ALT levels. These changes did not reflect the usual progression of the disease in ApoE Ϫ/Ϫ mice, since exacerbated liver injury was not present in untreated age-paired ApoE Ϫ/Ϫ mice. Moreover, hepatic cytochrome P-450 expression was unchanged in ApoE Ϫ/Ϫ mice. To explore potential mechanisms, cell types relevant to liver pathophysiology were exposed to selected cholesterol-oxidized products. Incubation of hepatocytes with a mixture of oxysterols representative of those detected by GC-MS in livers from ApoE Ϫ/Ϫ mice resulted in a concentration-dependent increase in total lipoperoxides and SOD activity. In hepatic stellate cells, oxysterols increased IL-8 secretion through a NF-B-independent mechanism and upregulated TIMP-1 expression. In macrophages, oxysterols increased TGF-␤1 secretion and MCP-1 expression in a concentration-dependent manner. Oxysterols did not compromise cell viability. Taken together, these findings demonstrate that hypercholesterolemic mice are sensitized to liver injury and that cholesterol-derived products (i.e., oxysterols) are able to induce proinflammatory and profibrogenic mechanisms in liver cells.

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“…The viability of all cell cultures utilized for study was 490%. For non-parenchymal cells, after in situ perfusion of the liver with 10 mg pronase (Boehringer Mannheim, Indianapolis, IN, USA) followed by collagenase (Crescent Chemical, Hauppauge, NY, USA) as described, 38 dispersed cell suspensions were layered on a discontinuous density gradient of 8.2 and 15.6% Accudenz (Accurate Chemical and Scientific, Westbury, NY, USA). Non-parenchymal cells containing endothelial cells and Kupffer cells in the lower layer were collected.…”

Section: Cell Isolation and Cell Surface Labelingmentioning

confidence: 99%

Endoplasmic reticulum stress, hepatocyte CD1d and NKT cell abnormalities in murine fatty livers

Yang

Jhaveri

Huang

et al. 2007

Laboratory Investigation

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The liver regulates lipid homeostasis and is enriched with natural killer T (NKT) cells that respond to lipid antigens. Optimal maturation and activation of NKT cells requires their interaction with lipid antigens that are presented by cluster of differentiation-1 (CD-1) molecules on antigen-presenting cells. Hepatocytes express CD1d and present lipid antigens to NKT cells. Depletion and dysregulation of hepatic NKT cells occurs in mice with fatty livers. Herein, we assess whether reduced CD1d content on steatotic hepatocytes contributes to fatty liver-associated NKT cell abnormalities. We show that despite expressing normal levels of CD1d mRNA, fatty hepatocytes from ob/ob mice have significantly less CD1d on their plasma membranes than normal hepatocytes. This has functional significance because ob/ob hepatocytes are less able to activate CD1d-restricted T-cell responses in vitro, and CD1d-reactive NKT cells are reduced in ob/ob livers. Events in the endoplasmic reticulum (ER) normally regulate CD1d trafficking to plasma membranes. Hepatic steatosis has been associated with ER stress. To determine if ER stress reduces CD-1 accumulation on hepatocytes, we evaluated hepatic ER stress in ob/ob mice and treated cultured hepatocytes and lean mice with tunicamycin to induce ER stress. Lipid accumulation and ER stress occurred in the livers of both ob/ob and tunicamycin-treated mice. Tunicamycin caused dose-dependent decreases in hepatocyte CD1d, inhibited hepatocyte activation of CD1d-restricted T-cell responses, depleted liver populations of CD1d-reactive NKT cells and promoted Th-1 polarization of hepatic cytokine production. In conclusion, ER stress-related decreases in hepatocyte CD1d contribute to NKT cell dysregulation in fatty livers.

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NF-κB activation in Kupffer cells after partial hepatectomy

Cited by 51 publications

References 31 publications

A critical appraisal of the hemodynamic signal driving liver regeneration

A critical appraisal of the hemodynamic signal driving liver regeneration

Increased susceptibility to exacerbated liver injury in hypercholesterolemic ApoE-deficient mice: potential involvement of oxysterols

Endoplasmic reticulum stress, hepatocyte CD1d and NKT cell abnormalities in murine fatty livers

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