Eicosanoids and the gastrointestinal tract

Eberhart, Charles E.; DuBois, Raymond N.

doi:10.1016/0016-5085(95)90296-1

Cited by 368 publications

(226 citation statements)

References 194 publications

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“…pylori possesses several different phospholipase (PL) activities, such as PLA 1 , PLA 2 and PLC [45]. The main activities of these PLs are thought to be the degradation of the phospholipid components of the mucosal barrier and normal phospholipid bilayer of the epithelial cell membrane [46]; but it may also influence the synthesis of prostaglandin [47]. Phospholipids constitute c. 20% of the dry weight of the human gastric mucus and are believed to be important in generating a hydrophobic barrier and maintaining normal cell functions.…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori adherence to gastric epithelial cells: a role for non-adhesin virulence genes

Zhang¹,

Dorrell

Wren

et al. 2002

Journal of Medical Microbiology

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Helicobacter pylori is a major aetiological agent in gastroduodenal disorders and adherence of the bacteria to the gastric mucosa is one of the initial stages of infection. Although a number of specific adhesins has been identified, other H. pylori virulence factors may play a role in adherence to gastric epithelial cells directly or through interaction with other adhesins. This study assessed the effect of 16 H. pylori virulence factors on the adherence of the bacteria to gastric AGS cells and on gastric epithelial cell cycle distribution. Defined isogenic H. pylori SS1 mutants were used. After coincubation of gastric AGS cells and bacteria, adherence of H. pylori to AGS cells was visualised by immunofluorescence microscopy and quantified by flow cytometry. Cell cycle phase distribution was analysed by flow cytometry with propidium iodide staining. Mutants were tested for their ability to adhere to AGS cells and compared with the wild-type SS1 strain. Mutations in genes in the cag pathogenicity island showed that cagP and cagE mutants adhered less than the wild-type strain to AGS cells, whereas a cagF mutant showed no reduction in adherence. Mutations in genes involved in flagellar biosynthesis showed that the adherence ability of fliQ, f liM and fliS mutants was reduced, but a flhB mutant possessed wild-type levels of adherence. Mutations in genes coding for the urease (ureB) and phospholipase (pldA) enzymes did not affect adherence, but mutation of the tlyA gene encoding an H. pylori haemolysin resulted in a reduced adherence. A fliQ mutant, with reduced adherence to AGS cells, was less able to induce AGS cell apoptosis than SS1. The ability to induce G 0 G 1 cell cycle arrest was also abolished in the fliQ mutant. However, an increased cell number in S phase was observed when AGS cells were exposed to the fliQ mutant compared with SS1, suggesting that unattached bacteria may still be able to stimulate cell proliferation. In addition to known adhesins, other bacterial virulence factors such as CagE, CagP, FliQ, FliM, FliS and TlyA appear to play a role in H. pylori adherence to gastric epithelial cells. Mutations in these genes may affect H. pylori pathogenicity by reducing either the ability of the bacteria to attach to gastric epithelial cells or the intensity of bacteriahost cell interactions.

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Section: Discussionmentioning

confidence: 99%

Helicobacter pylori adherence to gastric epithelial cells: a role for non-adhesin virulence genes

Zhang¹,

Dorrell

Wren

et al. 2002

Journal of Medical Microbiology

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“…The cyclooxygenase (COX) enzyme catalyzes the conversion of arachidonic acid to prostaglandins (11). Two COX isoforms have been identified in humans, COX-1 and COX-2.…”

Section: Introductionmentioning

confidence: 99%

“…COX-1 is a constitutively expressed enzyme, present in most tissues including the gastrointestinal tract, considered to be a housekeeping gene involved in general cell functions. COX-2 is an inducible enzyme usually undetectable in most tissues, upregulated in response to various stimuli, including growth factors, tumor promoters and cytokines (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Over-expression of cyclooxygenase-2 in endoscopic biopsies of ectopic gastric mucosa

Martins

Neto

Oshima

et al. 2007

Braz J Med Biol Res

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Ectopic gastric mucosa (EGM) is considered to be a congenital condition. Rare cases of adenocarcinoma have been described. There are no data justifying regular biopsies or follow-up. Cyclooxygenase-2 (COX-2) is a protein involved in gastrointestinal tumor development by inhibiting apoptosis and regulating angiogenesis. The aim of this prospective study was to evaluate COX-2 expression in EGM and compare it with normal tissue and Barrett's esophagus. We evaluated 1327 patients. Biopsies were taken from the inlet patch for histological evaluation and from the gastric antrum to assess Helicobacter pylori infection. Biopsies taken from normal esophageal, gastric antrum and body mucosa and Barrett's esophagus were retrieved from a tissue bank. EGM biopsies were evaluated with respect to type of epithelium, presence of H. pylori, and inflammation. COX-2 was detected by immunohistochemistry using the avidin-biotin complex. EGM islets were found in 14 patients (1.1%). Histological examination revealed fundic type epithelium in 58.3% of cases, H. pylori was present in 50% and chronic inflammation in 66.7%. Expression of COX-2 was negative in normal distal esophagus, normal gastric antrum and normal gastric body specimens (10 each). In contrast, EGM presented over-expression of COX-2 in 41.7% of cases and Barrett's esophagus in 90% of cases (P = 0.04 and 0.03, respectively). COX-2 immunoexpression in EGM was not related to gender, age, epithelium type, presence of inflammation or intestinal metaplasia, H. pylori infection, or any endoscopic finding. Our results demonstrate up-regulation of COX-2 in EGM, suggesting a possible malignant potential of this so-called harmless mucosa.

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“…Three-day treatment with celecoxib at low (2.5 -5 mg ml À1 ) concentrations resulted in less than 40% of cell viability and more than 50% of floating cells; after treatment with higher celecoxib concentrations (25 -50 mg ml À1 ), most of the cells were floating and dead (not shown). Since the proportion of floating to adherent cells was found to be a measure of apoptosis (Eberhart and DuBois, 1995), the HTC-IR cell growth inhibition by celecoxib was likely to take place through the induction of apoptosis.…”

Section: Resultsmentioning

confidence: 99%

“…While COX-1 is a constitutively expressed enzyme that is generally involved in cell function of most tissues, COX-2 is an inducible enzyme in response to cellular stimuli, including mitogens, tumour promoters, cytokines, and other inflammatory mediators (Eberhart and DuBois, 1995;Smith et al, 1996;Beejay and Wolfe, 1999;Whittle et al, 2000). Although the molecular mechanisms causing the overexpression of COX-2 in various cancer cells are not understood, it is known that increased level of COX-2 results in enhanced PG production.…”

mentioning

confidence: 99%

Do altering in ornithine decarboxylase activity and gene expression contribute to antiproliferative properties of COX inhibitors?

et al. 2003

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Two isoforms of cyclooxygenase (COX) participate in growth control; COX-1 is constitutively expressed in most cells, and COX-2 is an inducible enzyme in response to cellular stimuli. An induction of COX-2 found in neoplastic tissues results in increased cell growth, inhibition of apoptosis, activation of angiogenesis, and decreased immune responsiveness. Although both COX-1 and COX-2 inhibitors are suppressors of cell proliferation and appear to be chemopreventive agents for tumorigenesis, the molecular mechanisms mediating antiproliferative effect of COX inhibitors are still not well defined. This study contrasts and compares the effects of aspirin and celecoxib, inhibitors of COX-1 and COX-2, in rat hepatoma HTC-IR cells. The following were assessed: cell proliferation and apoptosis, ornithine decarboxylase (ODC) activity, and pattern expression of three immediate-early genes, c-myc, Egr-1, and c-fos. We have shown that the treatment of hepatocytes in vitro with the selective COX-2 inhibitor, celecoxib, was associated with induction of apoptosis and complete inhibition of cellular proliferation. Aspirin exhibited a small antiproliferative effect that was not associated with apoptosis. Treatment with celecoxib produced dose-and time-dependent decrease in ODC activity. In addition, at higher drug concentration the decrease in ODC activity was greater in proliferating than in resting cells. Much lesser inhibitory effect on ODC activity was observed in aspirin-treated cells. The two COX inhibitors did not change c-myc expression, significantly decreased the expression of Egr-1, and differentially altered expression of c-fos; aspirin did not change, but celecoxib dramatically decreased the levels of c-fos-mRNA. Our study revealed that celecoxib and aspirin share the ability to inhibit ODC activity and alter the pattern of immediate-early gene expression. It seems that some of the observed effects are likely to be related to COX-independent pathways. The precise mechanisms of action of COX inhibitors should be defined before using these drugs for cancer chemopreventive therapy.

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Eicosanoids and the gastrointestinal tract

Cited by 368 publications

References 194 publications

Helicobacter pylori adherence to gastric epithelial cells: a role for non-adhesin virulence genes

Helicobacter pylori adherence to gastric epithelial cells: a role for non-adhesin virulence genes

Over-expression of cyclooxygenase-2 in endoscopic biopsies of ectopic gastric mucosa

Do altering in ornithine decarboxylase activity and gene expression contribute to antiproliferative properties of COX inhibitors?

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