Restriction of gut-derived endotoxin impairs DNA synthesis for liver regeneration

Cornell, R. P.

doi:10.1152/ajpregu.1985.249.5.r563

Cited by 48 publications

(53 citation statements)

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“…A possible role of TNF-a in triggering in the liver of Rel-B 0 / 0 mice. 38 As far as the faster mobility complex is concerned, it is possible that it could represent a liver cell proliferation has been supported recently by the following: 1) germ-free rats show delayed regeneration of heterodimer p35/p50 resulting from the turnover of nuclear p65, via a degradative mechanism that converts it to p35 with the liver after PH 41 ; 2) anti-TNF-a antibodies inhibit liver regeneration after hepatectomy 6 ; 3) treatment with recombikB binding activity, as suggested by Cressman and Taub.…”

Section: Methodsmentioning

confidence: 99%

Liver Cell Proliferation Induced by Nafenopin and Cyproterone Acetate Is Not Associated With Increases in Activation of Transcription Factors Nf–κB and Ap–1 or With Expression of Tumor Necrosis Factor α

et al. 1997

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The unique ability of the liver to regenerate after partial Our previous studies have shown a different pattern of removal or injury has been of interest to investigators for immediate early gene and growth factor gene expression many years. Although considerable advances have been made between compensatory liver regeneration occurring in understanding the molecular mechanisms that control after cell loss/death and direct hyperplasia induced by liver cell growth, the exact nature of the stimuli involved in primary mitogens. In the present study, modifications the initiation and progression of the cell cycle has remained in the activation of two transcription factors, NF-kB and elusive. Activation of preexisting latent transcription factors AP-1; steady-state levels of tumor necrosis factor a (TNFrecently has been claimed to play a major role in making a) messenger RNA (mRNA); and induction of the inducthe hepatocytes competent to proliferate (priming effect), 1 ible nitric oxide synthase (iNOS) were examined in rat presumably via induction of the hepatic expression of several liver during different types of cell proliferation. Compensatory regeneration was induced in male Wistar rats immediate early genes considered to be related to cell cycle.2 by partial hepatectomy of two thirds (PH) or a necro-One such transcription factor is NF-kB. NF-kB refers to memgenic dose of CCl 4 (2 mL/kg), whereas direct hyperpla-bers of a Rel family of transcription factors that were identisia was induced by a single administration of the pri-fied for their ability to bind and transactivate the enhancer mary mitogens lead nitrate (LN, 100 mmol/kg), of immunoglobulin k gene in B cells. More recently, a role cyproterone acetate (CPA, 60 mg/kg), or nafenopin for NF-kB in liver regeneration was suggested based on the (NAF, 200 mg/kg). Liver regeneration after treatment finding of a strong induction of DNA binding by NF-kB (p65/ with CCl 4 was associated with an increase in steady-p50 heterodimer), p50/p50 homodimers, and posthepatecstate levels of TNF-a mRNA, activation of NF-kB and tomy factor within 30 minutes after partial hepatectomy of AP-1, and induction of iNOS. A strong and prolonged two thirds (PH).3,4 One of the most powerful inducers of NFactivation of NF-kB but not of AP-1 was observed in LN-kB is tumor necrosis factor a (TNF-a).5 This cytokine, which induced hyperplasia. LN also induced an increase in he-is involved in several pathophysiological processes, has been patic levels of TNF-a and iNOS mRNA. On the other suggested to play a major role in liver cell proliferation based hand, direct hyperplasia induced by two other primary on the following: 1) pretreatment with anti-TNF-a antibodmitogens, NAF and CPA, occurred in the complete ab-ies inhibits liver regeneration after PH 6 ; 2) a rapid increase sence of modifications in the hepatic levels of TNF-a in TNF-a messenger RNA (mRNA) is observed during liver mRNA, activation of NF-kB and AP-1, or induction of cell proliferation induced by some primary mitogens 7,8 ; and iN...

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Section: Methodsmentioning

confidence: 99%

Liver Cell Proliferation Induced by Nafenopin and Cyproterone Acetate Is Not Associated With Increases in Activation of Transcription Factors Nf–κB and Ap–1 or With Expression of Tumor Necrosis Factor α

et al. 1997

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“…46,47 The signal transduction pathway through TNFR-1 after PH is only one of a complex circuitry involving other cytokines, nitric oxide, and endotoxin (lipopolysaccharide, LPS) released from blood. [70][71][72][73] Expression of immediate early genes and transcription-factor activation is followed by expression of cellcycle-related genes (Fig. 2).…”

Section: Gene Expression Cytokines and Growth Factors In The Regenementioning

confidence: 99%

Liver regeneration: From laboratory to clinic

Fausto

2001

Liver Transplantation

127

114

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“…In addition, defined-flora rats with reduced enteric gram-negative bacterial populations demonstrated depression of hepatic DNA replication during liver regeneration after 67% liver resection (3). To rigorously test our hypothesis for liver regeneration, [' HI thymidine incorporation into hepatic DNA after partial hepatectomy of germ-free (GF) BALB/c mice was compared with conventional (CV) control animals.…”

mentioning

confidence: 99%

Depressed Liver Regeneration After Partial Hepatectomy of Germ–Free, Athymic and Lipopolysaccharide–Resistant Mice

1990

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A hypothesis has been proposed by this laboratory that endogenous gut-derived lipopolysaccharide is responsible for systemic endotoxemia in animals with acute liver injury particularly after partial (67%) hepatectomy. Systemic lipopolysaccharide and possibly fibrin aggregates or tissue debris then elicit release of cytokines from phagocytizing macrophages and/or monocytes that may be essential for normal liver regeneration. To test this hypothesis liver regeneration was assessed in germ-free euthymic mice that lack the gram-negative bacterial source of lipopolysaccharide, as well as being deficient in lymphoid tissue and relatively resistant to endotoxin. To complement the germ-free animals, conventional athymic nude BALB/c mice and conventional lipopolysaccharide-resistant C3H/HeJ mice were also examined. Liver regeneration, quantified by [3H] thymidine incorporation into hepatic DNA after partial hepatectomy was performed on mice anesthetized with ether, was significantly depressed in germ-free euthymic and conventional athymic BALB/c mice and delayed in conventional lipopolysaccharide-resistant C3H/HeJ mice, as compared with conventional control BALB/c and C3H/HeN animals. Pretreatment of conventional euthymic control mice with lipopolysaccharide 24 hr before surgery significantly stimulated hepatic DNA synthesis after 67% liver resection. Germ-free euthymic, conventional athymic, and conventional lipopolysaccharide-resistant mice pretreated with endotoxin did not manifest significant stimulation of liver regeneration. Evidence is reviewed that cytokine release in response to endotoxin was depressed in germ-free euthymic, conventional athymic, and conventional lipopolysaccharide-resistant mice as compared with conventional euthymic controls.(ABSTRACT TRUNCATED AT 250 WORDS)

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Restriction of gut-derived endotoxin impairs DNA synthesis for liver regeneration

Cited by 48 publications

References 0 publications

Liver Cell Proliferation Induced by Nafenopin and Cyproterone Acetate Is Not Associated With Increases in Activation of Transcription Factors Nf–κB and Ap–1 or With Expression of Tumor Necrosis Factor α

Liver Cell Proliferation Induced by Nafenopin and Cyproterone Acetate Is Not Associated With Increases in Activation of Transcription Factors Nf–κB and Ap–1 or With Expression of Tumor Necrosis Factor α

Liver regeneration: From laboratory to clinic

Depressed Liver Regeneration After Partial Hepatectomy of Germ–Free, Athymic and Lipopolysaccharide–Resistant Mice

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