Endotoxin-induced liver injury after extended hepatectomy and the role of kupffer cells in the rat

Nagata, Yusuke; Tanaka, N; Orita, Kunzo

doi:10.1007/bf01427038

Cited by 20 publications

(17 citation statements)

References 22 publications

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“…These factors are considered to play an important role in liver injury [16,17]. TNF-a is the initial and most important mediator of cytokine cascade in sepsis [30,31].…”

Section: Discussionmentioning

confidence: 99%

“…LPS has a direct activating effect on Kupffer cells by causing the release of various inflammatory mediators including tumor necrosis factor (TNF)-a, interleukin (IL)-1b, IL-6, interferon (IFN)-g, cytokine-induced neutrophil chemoattractant (CINC), and nitric oxide [10 -15]. These mediators are causative of liver injury, individually or by forming a network [16,17].…”

Section: Introductionmentioning

confidence: 99%

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Pirfenidone prevents endotoxin-induced liver injury after partial hepatectomy in rats

Tsuchiya

Kaibori

Yanagida

et al. 2004

Journal of Hepatology

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“…These factors are considered to play an important role in liver injury [16,17]. TNF-a is the initial and most important mediator of cytokine cascade in sepsis [30,31].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pirfenidone prevents endotoxin-induced liver injury after partial hepatectomy in rats

Tsuchiya

Kaibori

Yanagida

et al. 2004

Journal of Hepatology

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“…During liver regeneration, EGFP expression was observed after 12 h, and expression was primarily located in Kupffer cells. Kupffer cells are generally presumed to be an important source of hepatic TNF-␣ during an inflammatory response (23). After PH, depletion of Kupffer cells using CI 2 MDP-liposomes abolishes hepatic-derived IL-6 and hepatic growth factor mRNA synthesis, well-known stimulators for hepatic regeneration process (6,16,21), and decreases hepatic expression of TNF-␣ (22).…”

Section: Discussionmentioning

confidence: 99%

NF-κB activation in Kupffer cells after partial hepatectomy

Yang

Magness

Bataller

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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The transcription factor nuclear factor-κB (NF-κB) is activated during liver regeneration after partial hepatectomy. However, the physiological role and cellular localization of NF-κB activation are unresolved. In this study, we used an adenoviral vector expressing a mutated form of IκBα to inhibit NF-κB activity during liver regeneration. After partial hepatectomy in mice, introduction of Ad5IκB, but not a control virus (Ad5GFP), resulted in increased liver injury and decreased hepatocyte proliferation. Hepatocyte apoptosis was not observed. To investigate the kinetics and cellular localization of NF-κB-induced transcription during liver regeneration, we generated a transgenic mouse expressing enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-κB cis elements ( cis-NF-κB-EGFP). During liver regeneration, EGFP expression was detected within 12 h and was primarily located in Kupffer cells. Our data demonstrate that activation of NF-κB initially occurs in Kupffer cells after partial hepatectomy in mice.

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“…Thus, despite increased expression of cytokines (i.e., TNF and IL-1b) that are generally considered to be ''proinflammatory'' and which can cause apoptosis, 2 hepatocyte death was not increased after PH, even in GdCl-treated rats. Interestingly, although Kupffer cells are thought to produce TNF in the diseased liver, 5,6 in situ RT-PCR experiments suggest that these cells are not major sources of TNF in the regenerating liver. Rather, TNF expression is confined to portal structures and hepatic venous endothelium in both control (Fig.…”

mentioning

confidence: 99%

Kupffer cell depletion abolishes induction of interleukin-10 and permits sustained overexpression of tumor necrosis factor alpha messenger RNA in the regenerating rat liver

et al. 1997

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that synchronize the regenerative response to liver injury Tumor necrosis factor a (TNF), initiates a cytokine and implies that hepatocytes and liver nonparenchymal cells cascade that promotes hepatocyte proliferation after are both the sources of, and the targets for, various growth-70% partial hepatectomy (PH) but the mechanisms reguregulatory cytokines. Thus, to understand how liver regenerlating TNF production after PH are unknown. We preation is regulated, it is critical to delineate the cytokine netviously reported that gadolinium chloride (GdCl), an works that modify the phenotypes of liver cells during this agent that depletes the liver of phagocytically active growth response. Kupffer cells, enhances hepatic expression of TNF mesSeveral lines of evidence suggest that tumor necrosis factor senger RNA (mRNA) and promotes liver regeneration (TNF) a, is likely to be a key component of the paracrine after subsequent PH. This suggests that GdCl interferes network that promotes hepatocyte proliferation during liver with Kupffer cell mechanisms that normally constrain TNF production after PH. To evaluate this, the pre-and regeneration. The possibility that TNF may play a hepatopost-PH expression of TNF, TNF-inducible cytokines (in-trophic role is somewhat counterintutitive, given its wellterleukin [IL]-1, IL-6) and cytokines (transforming documented cytotoxic effects in other settings.2 However, this growth factor [TGF] b 1 and IL-10) that down-regulate theory is supported by data which show that liver DNA syn-TNF were compared in controls and GdCl-treated rats. thesis and hepatocyte mitoses increase in healthy adult rats In controls, TNF, IL-1, IL-6, and IL-10 increase within 3 after intravenous administration of human recombinant hours after PH, whereas TGF-b 1 is induced much later TNF 3 and evidence that pretreatment of rats with neutraliz-(ú24 hours after PH). GdCl causes sustained overex-ing antibodies to TNF 4 or soluble TNF receptors (Rai RM, et pression of TNF mRNA and transient overexpression of al., Unpublished data, May 1996) inhibits hepatocyte DNA circulating TNF protein after PH; both TNF-inducible synthesis after PH. To date, the mechanisms which control cytokines are also relatively overexpressed. Cytokines TNF production during liver regeneration have not been that down-regulate TNF are effected differentially by characterized. GdCl. Regenerative induction of IL-10 is abolished butIsolated Kupffer cells are known to produce TNF when TGF-b 1 induction is unaltered. Because IL-10 is known to stimulated by lipopolysaccharide 5 and are generally preshorten the half-life of TNF mRNA, these results suggest sumed to be an important source of hepatic TNF during an that Kupffer cell production of IL-10 is an important inflammatory response.6 Thus, we were surprised to discover mechanism that down-regulates TNF production during that gadolinium chloride (GdCl), an agent that depletes the liver regeneration. (HEPATOLOGY 1997;25:889-895.) liver of phagocytically active Kupffer cells, 7 increases hepatic l...

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Endotoxin-induced liver injury after extended hepatectomy and the role of kupffer cells in the rat

Cited by 20 publications

References 22 publications

Pirfenidone prevents endotoxin-induced liver injury after partial hepatectomy in rats

Pirfenidone prevents endotoxin-induced liver injury after partial hepatectomy in rats

NF-κB activation in Kupffer cells after partial hepatectomy

Kupffer cell depletion abolishes induction of interleukin-10 and permits sustained overexpression of tumor necrosis factor alpha messenger RNA in the regenerating rat liver

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