Model bile and bile salts accelerate mucin secretion by cultured dog gallbladder epithelial cells

Klinkspoor, J. H.; Kuver, Rahul; Savard, Christopher E.; Oda, Dolphine; Azzouz, Hatem; Tytgat, G. N. J.; Groen, Albert K.; Lee, S P

doi:10.1016/0016-5085(95)90293-7

Cited by 60 publications

(60 citation statements)

References 26 publications

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“…40,41 Upregulation of these genes could lead to increased gallbladder mucin concentrations. Although mucin secretion has been suggested to be stimulated by cholesterol supersaturation, 22 hydrophobic bile salts, 42 or gallbladder wall inflammation, 43 we found no differences between pancreatitis and symptomatic gallstone patients in this respect. On the other hand, pathobiological effects of gallstones on the gallbladder mucosa could affect mucin secretion.…”

Section: Discussioncontrasting

confidence: 62%

Small gallstones, preserved gallbladder motility, and fast crystallization are associated with pancreatitis†‡

et al. 2005

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Acute pancreatitis is a severe complication of gallstones with considerable mortality. We sought to explore the potential risk factors for biliary pancreatitis. We compared postprandial gallbladder motility (via ultrasonography) and, after subsequent cholecystectomy, numbers, sizes, and types of gallstones; gallbladder bile composition; and cholesterol crystallization in 21 gallstone patients with previous pancreatitis and 30 patients with uncomplicated symptomatic gallstones. Gallbladder motility was stronger in pancreatitis patients than in patients with uncomplicated symptomatic gallstones (minimum postprandial gallbladder volumes: 5.8 ؎ 1.0 vs. 8.1 ؎ 0.7 mL; P ‫؍‬ .005). Pancreatitis patients had more often sludge (41% vs. 13%; P ‫؍‬ .03) and smaller and more gallstones than patients with symptomatic gallstones (smallest stone diameters: 2 ؎ 1 vs. 8 ؎ 2 mm; P ‫؍‬ .001). Also, crystallization occurred much faster in the bile of pancreatitis patients (1.0 ؎ 0.0 vs. 2.5 ؎ 0.4 days; P < .001), possibly because of higher mucin concentrations (3.3 ؎ 1.9 vs. 0.8 ؎ 0.2 mg/mL; P ‫؍‬ .04). No significant differences were found in types of gallstones, relative biliary lipid contents, cholesterol saturation indexes, bile salt species composition, phospholipid classes, total protein or immunoglobulin (G, M, and A), haptoglobin, and ␣-1 acid glycoprotein concentrations. In conclusion, patients with small gallbladder stones and/or preserved gallbladder motility are at increased risk of pancreatitis. The potential benefit of prophylactic cholecystectomy in this patient category has yet to be explored. (HEPATOLOGY 2005;41:738-746.)

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Section: Discussioncontrasting

confidence: 62%

Small gallstones, preserved gallbladder motility, and fast crystallization are associated with pancreatitis†‡

et al. 2005

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“…Mucin secretion by these cells has been extensively studied. In the cultured DGBE cells, mucin secretion was found to be stimulated by compounds that cause an increase in intracellular cAMP 12 or activate protein kinase C. 14 Bile salts were also shown to be potent stimulators of mucin secretion, 13,14 and overexpression of cystic fibrosis transmembrane regulator in these cells also caused an increase in mucin secretion. 21 In the present study, we found that LPS derived from E. coli, K. pneumoniae, and P. aeruginosa are all effective stimulants of mucin secretion.…”

Section: Discussionmentioning

confidence: 99%

“…12 We also showed that bile salts can act as intraluminal secretagogues of mucin secretion. 13 Subsequent studies showed that multiple intracellular second-messenger pathways are involved in the regulation of mucin secretion by the gallbladder epithelium. In addition to an increase in intracellular cAMP, activation of protein kinase C was also found to cause mucin hypersecretion by the dog gallbladder epithelial (DGBE) cells.…”

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confidence: 99%

Lipopolysaccharide From Escherichia Coli Stimulates Mucin Secretion by Cultured Dog Gallbladder Epithelial Cells

et al. 1999

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Biliary infection is associated with mucin hypersecretion by the biliary epithelium. Mucins have been identified as potent pronucleators of cholesterol in bile. The aim of the present study was to determine whether lipopolysaccharides (LPS) from different bacteria are capable of stimulating mucin secretion by cultured dog gallbladder epithelial (DGBE) cells, and to investigate the mechanism by which LPS stimulate mucin secretion. Mucin secretion by confluent monolayers of DGBE cells was quantified by measuring the secretion of [3H]-N-acetyl-D-glucosamine-labeled glycoproteins. Cell viability was evaluated by measuring the leakage of the enzyme, lactate dehydrogenase (LDH), into the culture medium. LPS, derived from Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa (200 g/mL), all caused an increase in mucin secretion by the DGBE cells, without causing concomitant cell lysis. LPS from E. coli was found to be the most potent stimulator of mucin secretion, and increased mucin secretion by the DGBE cells to 252% ؎ 14% of control. LPS from E. coli had no effect on intracellular cyclic adenosine monophosphate (cAMP) levels in the DGBE cells. Addition of the nitric oxide (NO)-releasing compound, NOR-4 (0.125-1 mmol/L), to the cells did not result in increased mucin secretion, and the NO synthase inhibitor, N -nitro-L-arginine methyl ester (L-NAME) (4 or 10 mmol/L), did not inhibit the LPSstimulated mucin secretion. Exogenous tumor necrosis factor ␣ (TNF-␣) (1-10 ng/mL) did cause a minor increase in mucin secretion by the DGBE cells, but the effect of LPS from E. coli on mucin secretion could not be inhibited by preincubation with a TNF-␣ antibody (10 g/mL). We conclude that LPS stimulates mucin secretion by the gallbladder epithelium. Whether this stimulation is mediated by TNF-␣ remains to be determined. (HEPATOLOGY 1999;29:1352-1357.)Gallbladder mucin, the primary glycoprotein secreted by the gallbladder, is a densely glycosylated macromolecule with a molecular mass of approximately 2 ϫ 10 6 d. Mucin is regarded as an important contributing factor to gallstone formation. [1][2][3] Mucin has been shown to be present in the nucleus of several types of gallstones, and a macromolecular complex of mucin and bilirubin has been identified as a major structural component of the gallstone matrix. 4,5 Purified human gallbladder mucin is capable of nucleating cholesterol crystals from human bile. 6 Gallbladder mucus hypersecretion and increased mucin concentration are common findings in nearly all animal models of cholesterol gallstone disease. Mucin hypersecretion precedes crystal or stone formation. 7,8 These findings suggest that increased mucin secretion plays a role in the initial stages of gallstone formation.We have reported the succesful long-term culturing and passaging of normal, well-differentiated gallbladder epithelial cells from the dog. 9 These cells form electrically leakproof monolayers and synthesize protein and mucous glycoprotein. They have been extensively studied with regard to water and ...

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“…Model bile was prepared as described (23). Briefly, taurocholic acid, dissolved in methanol and water [85:15 (vol/vol)] was mixed with lecithin (L-␣-phosphatidylcholine) and purified recrystallized cholesterol in chloroform.…”

Section: Methodsmentioning

confidence: 99%

“…The model bile was then diluted 1:10 in serum-free media (SFM) and sterilized through a 0.45-m filter. Confluent monolayers of GBEC were treated with model bile applied to the AP surface for 48 h. The model bile solution had a cholesterol saturation index (CSI) of 1.5 under the diluted conditions used when applied to the cell surface (23). The total lipid concentration of the model bile solution as applied to the cells was 1.5 g/dl.…”

Section: Methodsmentioning

confidence: 99%

Cultured gallbladder epithelial cells synthesize apolipoproteins A-I and E

Liu¹,

Tauscher²,

Seo³

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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Gallbladder epithelial cells (GBEC) are exposed to high and fluctuating concentrations of biliary cholesterol on their apical (AP) surface. GBEC absorb and efflux cholesterol, but the mechanisms of cholesterol uptake, intracellular trafficking, and efflux in these cells are not known. We previously reported that ATP binding cassette (ABC)A1 mediates basolateral (BL) cholesterol efflux in cultured polarized GBEC. In addition, the nuclear hormone receptors liver X receptor (LXR)α and retinoid X receptor (RXR) mediate both AP and BL cholesterol efflux. An interesting finding from our previous study was that apolipoprotein (apo)A-I applied to the AP surfaces of cells elicited BL ABCA1-mediated cholesterol efflux. Because ABCA1-mediated cholesterol efflux requires the presence of a cholesterol acceptor, we hypothesized that GBEC synthesize and secrete endogenous apo into the BL compartment. Here, we demonstrate that cholesterol loading of cells with model bile and AP apoA-I treatment is associated with an increase in the synthesis of apoE mRNA and protein. Furthermore, apoE is secreted into the BL compartment. LXRα/RXR ligands stimulate the synthesis of endogenous apoA-I mRNA and protein, as well as apoE mRNA. BL secretion of apoA-I is elicited by LXRα/RXR ligands. Therefore, GBEC synthesize apoA-I and -E and efflux cholesterol using ABCA1- and non-ABCA1- mediated pathways. These processes may alter gallbladder biliary cholesterol concentrations and thereby influence gallstone formation.

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Model bile and bile salts accelerate mucin secretion by cultured dog gallbladder epithelial cells

Cited by 60 publications

References 26 publications

Small gallstones, preserved gallbladder motility, and fast crystallization are associated with pancreatitis†‡

Small gallstones, preserved gallbladder motility, and fast crystallization are associated with pancreatitis†‡

Lipopolysaccharide From Escherichia Coli Stimulates Mucin Secretion by Cultured Dog Gallbladder Epithelial Cells

Cultured gallbladder epithelial cells synthesize apolipoproteins A-I and E

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