Tri-iodothyronine differentially induces Kupffer cell ED1/ED2 subpopulations

Gomes, Lígia Ferreira; Lorente, Sandra; Simon, Karin Argenti; Areco, Kelsy Catherina Nema; Araújo-Peres, Clóvis; Videla, Luis A.

doi:10.1016/j.mam.2004.02.018

Cited by 18 publications

(29 citation statements)

References 28 publications

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“…First, co-staining of CD68, a KCspecific marker, and TUNEL characteristic for apoptotic cells strongly suggest that these cells were apoptotic KCs, rather than KCs engulfing some apoptotic bodies of hepatocytes or neutrophils in response to liver injury, as phagocytosis by KCs such as CD68-positive cells (ED1 cells) was barely detectable. 29 Second, Fas-positive cells were found almost in hepatic sinusoids (Figure 4), in which CD68 was detected. This co-localization of Fas-positive cells, CD68, and TUNELdouble-positive KCs was consistent with a scenario that Fas, through Fas receptor pathway, medicates apoptosis of those KCs.…”

Section: Discussionmentioning

confidence: 96%

Kupffer cells are associated with apoptosis, inflammation and fibrotic effects in hepatic fibrosis in rats

Liu

Tao

Sun

et al. 2010

Laboratory Investigation

125

100

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Hepatocellular apoptosis, hepatic inflammation, and fibrosis are prominent features in chronic liver diseases. However, the linkage among these processes remains mechanistically unclear. In this study, we examined the apoptosis and activation of Kupffer cells (KCs) as well as their pathophysiological involvement in liver fibrosis process. Hepatic fibrosis was induced in rats by dimethylnitrosamine (DMN) or carbon tetrachloride (CCl4) treatment. KCs were isolated from normal rats and incubated with lipopolysaccharide (LPS) or from fibrotic rats. The KCs were stained immunohistochemically with anti-CD68 antibody, a biomarker for KC. The level of expression of CD68 was analyzed by western blot and real-time PCR methods. The apoptosis and pathophysiological involvement of KCs in the formation of liver fibrosis were studied using confocal microscopy. The mRNA and protein expression of CD68 were significantly increased in DMNand CCL4-treated rats. Confocal microscopy analysis showed that CD68-positive KCs, but not a-smooth muscle actin (SMA)-positive cells, underwent apoptosis in the liver of DMN-and CCL4-treated rats. It was also revealed that the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and CD68-double-positive apoptotic KCs located in the portal or fibrotic septa area were situated next to hepatic stellate cells (HSCs). Tumor necrosis factor-a (TNF-a) and KC co-localized in the liver in the neighbor of HSCs. The double a-SMA-and collagen type I-positive cells predominantly existed in fibrotic septa, and those cells were co-localized clearly with CD68-positive cells. Interestingly, some CD68 and Col (1) double positive, but completely negative for a-SMA, were found in the portal areas and hepatic sinusoids; this phenomenon was also validated in primary isolated KCs after 6 h LPS exposure or fibrotic rats in vitro. These results show that KCs are associated with hepatocellular apoptosis, inflammation, and fibrosis process in a liver fibrosis models.

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Section: Discussionmentioning

confidence: 96%

Kupffer cells are associated with apoptosis, inflammation and fibrotic effects in hepatic fibrosis in rats

Liu

Tao

Sun

et al. 2010

Laboratory Investigation

125

100

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“…This pro-oxidant state induced in the liver of experimental animals by thyroid hormone administration is considered as a mild redox alteration, considering the lack of occurrence of morphological changes in liver parenchyma, except for significant hyperplasia and hypertrophy of Kupffer cells ( Fig. 2A), the resident macrophages of the liver (29,39). In man, hyperthyroidism is characterized by significant changes in circulating parameters related to oxidative stress, including (i) higher levels of lipid peroxidation indicators (40)(41)(42)(43)(44)(45)(46)(47)(48)(49); (ii) enhancement in hydrogen peroxide and lipid hydroperoxide levels (49); and (iii) diminished levels of antioxidants such as a-tocopherol (41), coenzyme Q (44), ascorbic acid (41), and reduced thiols (42,46,50).…”

Section: T 3 -Induced Enhancement Of Liver O 2 Consumption and Oxidatmentioning

confidence: 99%

Hormetic responses of thyroid hormone calorigenesis in the liver: Association with oxidative stress

Videla

2010

IUBMB Life

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SummaryThyroid hormone (L-3,3 0 ,5-triiodothyronine, T 3 ) exerts calorigenic effects by accelerating mitochondrial O 2 consumption through transcriptional activation of respiratory genes, with consequent increased reactive oxygen species (ROS) production. In the liver, ROS generation occurs at different sites of hepatocytes and in the respiratory burst of Kupffer cells, triggering the activation of the transcription factors nuclear factor-jB, signal transducer and activator of transcription 3, and activating protein 1. Under these conditions, the redox upregulation of Kupffer cell-dependent expression of cytokines [tumor necrosis factor-a, interleukin (IL)-1, and IL-6] is achieved, which upon interaction with specific receptors in hepatocytes trigger the expression of antioxidant enzymes (manganese superoxide dismutase, inducible nitric oxide synthase), antiapoptotic proteins (Bcl-2), and acute-phase proteins (haptoglobin, b-fibrinogen). These responses and the promotion of hepatocyte and Kupffer cell proliferation observed represent hormetic effects re-establishing redox homeostasis, promoting cell survival, and protecting the liver against ischemia-reperfusion (IR) injury. It is proposed that hormesis underlying T 3 action may constitute a novel preconditioning strategy for IR injury during liver surgery in man or in liver transplantation using reduced-size grafts from living donors, considering that (i) with the exception of the controversial ischemic preconditioning, all other studied strategies have failed to reach the clinical setting and (ii) T 3 is a well-tolerated therapeutic agent that either lacks major adverse effects or has minimal and controlled side effects. IUBMBIUBMB Life, 62(6): [460][461][462][463][464][465][466] 2010

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“…ED9 antigen was expressed to a greater extent in the intermediate and large Kupffer cells compared to other macrophages, suggesting that these Kupffer cells were more responsive to endotoxin. Thus, Kupffer cells mature in a size-dependent manner [42,43]. …”

Section: Phenotypic Analysis Of Tissue Macrophages and Kupffermentioning

confidence: 99%

“…ED1 and ED2 antigens can be used to characterize Kupffer cell subpopulations [43]. Indeed, small ED1-positive cells are described as "small Kupffer cells," which are less mature hepatic macrophages.…”

Section: Heterogeneous Response To Endotoxin In Kupffer Cells and Othmentioning

confidence: 99%

Role of Kupffer Cells in Lung Injury in Rats Administered Endotoxin11

Kono

Fujii

Amemiya

et al. 2005

Journal of Surgical Research

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Tri-iodothyronine differentially induces Kupffer cell ED1/ED2 subpopulations

Cited by 18 publications

References 28 publications

Kupffer cells are associated with apoptosis, inflammation and fibrotic effects in hepatic fibrosis in rats

Kupffer cells are associated with apoptosis, inflammation and fibrotic effects in hepatic fibrosis in rats

Hormetic responses of thyroid hormone calorigenesis in the liver: Association with oxidative stress

Role of Kupffer Cells in Lung Injury in Rats Administered Endotoxin11

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