Administration of <i>Escherichia coli</i> endotoxin to rat increases liver mass and hepatocyte volume <i>in vivo</i>

Qian, Dalong; Brosnan, John T.

doi:10.1042/bj3130479

Cited by 24 publications

(19 citation statements)

References 36 publications

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“…Our findings agree with those of other reports showing that septicemia following parenteral administration of LPS of E. coli increased DNA synthesis in the small intestinal crypts of the rat (20). In addition, parenteral administration of LPS increased the volume of rat liver and the number of hepatocytes (19). Although these changes were suspected to be mediated by interleukin-1 (20) or TNFc~ (19), they are in good agreement with the direct stimulatory action of LPS on DNA synthe-BACTERIAL FACTORS STIMULATE CELL PROLIFERATION 4"7 sis reported herein.…”

Section: Discussionsupporting

confidence: 95%

Lipopolysaccharide of Escherichia coli, polyamines, and acetic acid stimulate cell proliferation in intestinal epithelial cells

Olaya

Neopikhanov

Uribe

1999

In Vitro Cell.Dev.Biol.-Animal

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Our aim was to examine whether lipopolysaccharide of Escherichia coli, polyamines of dietetic and/or bacterial origin, and products of the bacterial metabolism influence cell proliferation in epithelial cells from the colon and small intestine. Lipopolysaccharide of Escherichia coli 0111:B4 was incubated with cultures from human colonic mucosa. The mitoses were arrested with Vincristine and the total number of metaphases per crypt was counted. In addition, lipopolysaccharide was incubated with a human colonic epithelial cell line from adenocarcinoma (LS-123 cells) and with a nontransformed small intestinal cell line from germ-free rats (IEC-6 cells) for 24 h. In the last 4 h, the cells were labeled with tritiated thymidine. The cells were incubated with putrescine, cadaverine, and spermidine at 10(-11)-10(-3) M and with acetic acid (10(-5)-10(-1) M), acetaldehyde (10(-10)-10(-4) M) and ammonium chloride (1-20 mM). Lipopolysaccharide of Escherichia coli increased the number of arrested metaphases in human colonic crypts and DNA synthesis in L-123 and IEC-6 cells (P < 0.001). All polyamines increased DNA synthesis in the colonic and small intestinal cell lines, the effects being more marked for putrescine (P < 0.001). The higher concentrations of acetic acid increased DNA synthesis in both epithelial cell lines (P < 0.001). Acetaldehyde slightly decreased DNA synthesis in LS-123 cells at cytotoxic concentrations. Ammonium chloride did not significantly affect DNA synthesis. The final concentration of nonionized ammonia was less than 3%. It is concluded that lipopolysaccharides of Escherichia coli and intraluminal factors derived from microorganisms increase cell proliferation in human colonic crypts and intestinal epithelial cell lines.

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Section: Discussionsupporting

confidence: 95%

Lipopolysaccharide of Escherichia coli, polyamines, and acetic acid stimulate cell proliferation in intestinal epithelial cells

Olaya

Neopikhanov

Uribe

1999

In Vitro Cell.Dev.Biol.-Animal

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“…The effect of LPS in vivo on hepatic function is also well known. LPS increases liver mass and hepatocyte volume (44), as well as modulating the synthesis of acute-phase proteins through the release of cytokines (TNF-␣ and IL-6) (38,47).…”

Section: Discussionmentioning

confidence: 99%

“…The effects of LPS on hepatic metabolism and function of the host are well known (44). In contrast, the direct responses of hepatocytes to moderate doses of LPS are not well characterized.…”

Section: Effects Of Lps On Hepatocytes In Vitromentioning

confidence: 99%

Role of Toll-Like Receptors in Changes in Gene Expression and NF-κB Activation in Mouse Hepatocytes Stimulated with Lipopolysaccharide

et al. 2002

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The liver is an important site of host-microbe interaction. Although hepatocytes have been reported to be responsive to lipopolysaccharide (LPS), the global gene expression changes by LPS and mechanism(s) by which LPS stimulates cultured hepatocytes remain uncertain. Cultures of primary mouse hepatocytes were incubated with LPS to assess its effects on the global gene expression, hepatic transcription factors, and mitogen-activated protein (MAP) kinase activation. DNA microarray analysis indicated that LPS modulates the selective expression of more than 80 genes and expressed sequence tags. We have shown previously that hepatocytes express CD14, which is required both for uptake and responsiveness to LPS. In other cells, responsiveness to microbial products requires expression of Toll-like receptors (TLR) and their associated accessory molecules. Hepatocytes expressed TLR1 through TLR9 as well as MyD88 and MD-2 transcripts, as shown by reverse transcriptase PCR analysis, indicating that hepatocytes express all known microbe recognition molecules. The MAP kinase extracellular signal-regulated kinase 1/2 was phosphorylated in response to LPS in mouse hepatocytes, and the levels of phosphorylation were lower in hepatocytes from TLR4-null mice. NF-B activation was reduced in TLR4-mutant or -null hepatocytes compared to control hepatocytes, and this defect was partially restored by adenoviral transduction of mouse TLR4. Thus, hepatocytes respond to nanogram concentrations of LPS through a TLR4 response pathway.Lipopolysaccharide (LPS), a glycolipid constituent of the outer membrane of gram-negative bacteria, initiates signaling cascades in cells such as macrophages and endothelial cells, leading to the release of cytokines and other inflammatory mediators during sepsis. Excessive production of these mediators can cause septic shock and multiple organ failure (55).A decade ago, CD14, a 55-kDa glycoprotein and monocyte differentiation antigen, was identified as an important LPS recognition molecule (60). CD14 alone, however, is unable to transduce the intracellular LPS signal, since CD14 is only tethered to the cytoplasmic membrane by a glycosyl phosphatidylinositol anchor and lacks a membrane-spanning domain (17). Members of a family of proteins, the mammalian homologues of the Drosophila Toll protein, were found to act as transmembrane coreceptors to CD14 in the cellular response to LPS (34). These Toll-like receptors (TLR) contain ectodomains with leucine-rich repeats, and their intracellular motifs are highly homologous to intracellular signaling domains of interleukin-1 receptor type I (IL-1RI) and IL-1RI accessory protein (reviewed in reference 5). Following dimerization of the TLR, these domains attract the adapter protein MyD88, which in turn recruits the IL-1R-associated kinase. Following this association, IL-1R-associated kinase phosphorylates tumor necrosis factor receptor-associated factor 6, which in turn attracts two more protein tyrosine kinases, transforming growth factor beta-activated kinase 1 (TAK-1)...

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“…Calculations-Intracellular hepatic amino acid concentrations were calculated using published data from our laboratory on hepatic cellular spaces (31). The measured hepatic concentration for an amino acid is the sum of the amino acid in the intracellular fluid (ICF) and the amino acid in the extracellular fluid (ECF).…”

Section: Methodsmentioning

confidence: 99%

Hyperglucagonemia in Rats Results in Decreased Plasma Homocysteine and Increased Flux through the Transsulfuration Pathway in Liver

Jacobs¹,

Stead²,

Brosnan

et al. 2001

Journal of Biological Chemistry

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An elevated plasma level of homocysteine is a risk factor for the development of cardiovascular disease. The purpose of this study was to investigate the effect of glucagon on homocysteine metabolism in the rat. Male Sprague-Dawley rats were treated with 4 mg/kg/day (3 injections per day) glucagon for 2 days while control rats received vehicle injections. Glucagon treatment resulted in a 30% decrease in total plasma homocysteine and increased hepatic activities of glycine N-methyltransferase, cystathionine ␤-synthase, and cystathionine ␥-lyase. Enzyme activities of the remethylation pathway were unaffected. The 90% elevation in activity of cystathionine ␤-synthase was accompanied by a 2-fold increase in its mRNA level. Hepatocytes prepared from glucagon-injected rats exported less homocysteine, when incubated with methionine, than did hepatocytes of saline-treated rats. Flux through cystathionine ␤-synthase was increased 5-fold in hepatocytes isolated from glucagon-treated rats as determined by production of 14 CO 2 and ␣-[1-14 C]ketobutyrate from L-[1-14 C]methionine. Methionine transport was elevated 2-fold in hepatocytes isolated from glucagon-treated rats resulting in increased hepatic methionine levels. Hepatic concentrations of S-adenosylmethionine and S-adenosylhomocysteine, allosteric activators of cystathionine ␤-synthase, were also increased following glucagon treatment. These results indicate that glucagon can regulate plasma homocysteine through its effects on the hepatic transsulfuration pathway.An elevated plasma concentration of homocysteine, a sulfurcontaining amino acid derived from methionine, has been recognized as an independent risk factor for the development of vascular disease (1). Methionine is adenylated by methionine adenosyltransferase to form S-adenosylmethionine, an important biological methyl donor. Numerous methyltransferases catalyze the transfer of a methyl group from S-adenosylmethionine to a methyl acceptor, producing a methylated product and S-adenosylhomocysteine, which is subsequently hydrolyzed to form adenosine and homocysteine. Homocysteine has several possible fates: 1) remethylation to form methionine via either the cobalamin-dependent methionine synthase (using N 5 -methyltetrahydrofolate as a methyl donor) or betaine:homocysteine methyltransferase (using betaine as a methyl donor); 2) catabolism by the transsulfuration pathway, ultimately forming cysteine; 3) export to the extracellular space. Two vitamin B 6 -dependent enzymes comprise the transsulfuration pathway: cystathionine ␤-synthase, which condenses homocysteine with serine to form cystathionine, and cystathionine ␥-lyase, which cleaves cystathionine to cysteine, NH 4 ϩ , and ␣-ketobutyrate.Altered flux through the remethylation or transsulfuration pathways as a result of genetic mutations or impaired vitamin status has been shown to affect plasma homocysteine levels (2, 3). In recent years it has also become apparent that certain hormones can affect homocysteine metabolism. It has been shown that hypothyroid ...

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Administration of Escherichia coli endotoxin to rat increases liver mass and hepatocyte volume in vivo

Cited by 24 publications

References 36 publications

Lipopolysaccharide of Escherichia coli, polyamines, and acetic acid stimulate cell proliferation in intestinal epithelial cells

Lipopolysaccharide of Escherichia coli, polyamines, and acetic acid stimulate cell proliferation in intestinal epithelial cells

Role of Toll-Like Receptors in Changes in Gene Expression and NF-κB Activation in Mouse Hepatocytes Stimulated with Lipopolysaccharide

Hyperglucagonemia in Rats Results in Decreased Plasma Homocysteine and Increased Flux through the Transsulfuration Pathway in Liver

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