TNFα stimulates mucus secretion in gallbladder epithelial cells

Ch, Cheung; Moore, EW; Prystowsky, JB; Rege, RV

doi:10.1016/s0016-5085(98)84969-x

Cited by 4 publications

(3 citation statements)

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“…TNF-α modulates many factors within the epithelium including mucus secretion, paracellular flow via tight junction control and is a master regulator of intracellular signaling cascades involved in cell survival, apoptosis, and proliferation, positioning it at the forefront of many inflammatory diseases and cancer studies. [45][46][47][48] TNF-α is therefore notably important in the maintenance and healing of the intestinal mucosa but is also important in guiding cell recruitment and function with anti-TNF trials of Adalimumab (Humira™) evidencing TNF-α as a target for mucosal healing in Crohn's patients. 49 We have demonstrated that LPS from specific species of bacteria can differentially modulate the production of TNF-α through individual profiles of activation of an NF-kB promoter.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharides modulate intestinal epithelial permeability and inflammation in a species-specific manner

2019

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Patients presenting with Inflammatory bowel disease have been shown to exhibit an altered microbiome in both Crohn's disease and Ulcerative colitis. This shift in the microbial content led us to question whether several of these microbes are important in inflammatory processes present in these diseases and more specifically whether lipopolysaccharides from the gram-negative cell wall differentially stimulates resident cells. We, therefore, investigated the possible contribution of five major species of gram-negative bacteria found to be altered in presence during disease progression and evaluate their pathogenicity through LPS. We demonstrated that LPS from these different species had individual capacities to induce NF-κB and pro-inflammatory IL-8 production from HEK-TLR4 cells in a TLR4 dependent manner. Additional work using human intestinal colonic epithelial cell monolayers (Caco-2) demonstrated that the cells responded to the serotype specific LPS in a distinct manner, inducing many inflammatory mediators such as TNF-α and IL-10 in significantly altered proportions. Furthermore, the permeability of Caco-2 monolayers, as a test for their ability to alter intestinal permeability, was also differentially altered by the serotype specific LPS modulating trans-epithelial electrical resistance, small molecule movement, and tight junction integrity. Our results suggest that specific species of bacteria may be potentiating the pathogenesis of IBD and chronic inflammatory diseases through their serotype specific LPS responses.

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Section: Discussionmentioning

confidence: 99%

Lipopolysaccharides modulate intestinal epithelial permeability and inflammation in a species-specific manner

2019

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“…32 Also, in human airway epithelium, mucin secretion and MUC-2 gene expression were found to be induced by TNF-␣. 33 More recently, TNF-␣ has been implicated in the regulation of mucin secretion in the human gallbladder 34,35 and human colon cancer 36 cells. We have recently shown that cultured mouse gallbladder epithelial cells secrete TNF-␣, and that when incubated with LPS, TNF-␣ secretion by these cells actually increases 37 (Savard CE et al, manuscript in preparation).…”

Section: Discussionmentioning

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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“…Despite these studies, the role of prostaglandins remains controversial, since no effect on mucin secretion was reported by others (99) and, in human clinical studies in which non-steroidal anti-inflammatory drugs were administered to patients on rapid-weight reducing diets (100) or after gallstone dissolution therapy (101), no reduction of the risk of gallstone development was observed. The influence of other biliary constituents, such as lysophosphatidylcholine (98), tumour necrosis factor alpha (102,103) and cholesterol, on mucin secretion has also been studied. Accumulation of cholesterol in gallbladder wall has been shown to decrease membrane fluidity of biliary epithelia and, perhaps, increase generation of NO (83) by induction of inducible NO synthase, which is the principle isoform of NO synthetase expressed in the gallbladder (104).…”

Section: Biliary Proteins Involved In Regulation Of Cholesterol Nuclementioning

confidence: 99%

Role of biliary proteins and non-protein factors in kinetics of cholesterol crystallisation and gallstone growth

Jirsa

Groen²

2001

Front Biosci

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Numerous biliary proteins as well as non-protein factors influence kinetics of cholesterol crystallisation from supersaturated bile. Cholesterol crystallisation pathways, methods used for quantitative evaluation of liquid-to-solid transition of cholesterol in bile and the classical concept of nucleation defect in pathogenesis of gallstones are reviewed in the first part of this article. The relevance of individual biliary proteins and non-protein factors is discussed in the second part. Finally, a new concept according to which accelerated crystallisation of cholesterol inhibits gallstone growth and protects the gallbladder wall from toxic injury resulting from the increased absorption and accumulation of cholesterol from supersaturated bile is suggested.

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TNFα stimulates mucus secretion in gallbladder epithelial cells

Cited by 4 publications

References 0 publications

Lipopolysaccharides modulate intestinal epithelial permeability and inflammation in a species-specific manner

Lipopolysaccharides modulate intestinal epithelial permeability and inflammation in a species-specific manner

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

Role of biliary proteins and non-protein factors in kinetics of cholesterol crystallisation and gallstone growth

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