Gastric Mucosal Proliferation Research Articles

PGE2/EP4 receptor attenuated mucosal injury via β‐arrestin1/Src/EGFR‐mediated proliferation in portal hypertensive gastropathy

Background and PurposePortal hypertensive gastropathy (PHG) is a serious complication of liver cirrhosis and a potential cause of bleeding in patients with cirrhosis. Suppressed mucosal epithelial proliferation is a crucial pathological characteristic of PHG. Our studies demonstrated an important role for PGE2 and its EP4 receptor in the promotion of mucosal proliferation. However, whether β‐arrestin1 (β‐arr1), a well‐established mediator of GPCRs, is involved in the PGE2/EP4 receptor‐mediated mucosal proliferation complex in PHG remains unclear. The aim of the study was to investigate whether β‐arr1 participated in PGE2/EP4 receptor‐mediated mucosal proliferation by recruiting the Src/EGF receptor (EGFR) complex to activate Akt/proliferating cell nuclear antigen (PCNA) signalling in PHG.Experimental ApproachGastric mucosal proliferation was examined in patients with PHG and the PHG model of β‐arr1‐knockout (β‐arr1‐KO) and β‐arr1‐wild type (β‐arr1‐WT) mice. The induction of β‐arr1 and EP4 receptor expression and the Src/EGFR signalling elements was investigated, and the mechanisms underlying PGE2‐regulated gastric mucosal proliferation were analysed.Key ResultsPortal hypertension suppressed COX‐1 but not COX‐2, which was accompanied by a down‐regulation of PGE2 generation and EP4 receptor levels in the mucosa of patients with PHG. PGE2 administration markedly promoted mucosal proliferation in a mouse model of PHG. Targeted deletion of β‐arr1 abolished PGE2/EP4 receptor‐mediated gastric proliferation in PHG by repressing the Src/EGFR/Akt/PCNA signalling network.Conclusions and ImplicationsThese results indicate that β‐arr1 regulates PGE2/EP4 receptor‐mediated mucosal proliferation by promoting activation of the Src/EGFR/Akt/PCNA signalling pathway, and thus, this network is a potential therapeutic target for PHG.

MOXIBUSTION ALLEVIATES GASTRIC PRECANCEROUS LESIONS IN RATS BY PROMOTING CELL APOPTOSIS AND INHIBITING PROLIFERATION-RELATED ONCOGENES.

Background:It is well known that gastric mucosa dysplasia and intestinal metaplasia are gastric precancerous lesions (GPL). Moxibustion treatment of Liangmen (ST21) and Zusanli (ST36) alleviated the inflammatory response and dysplasia of gastric mucosa in our previous study. The purpose of this study was to further examine the underlying mechanism of moxibustion treatment of ST21 and ST36 on GPL.Materials and Methods:Sixty SD rats were divided into five groups and rats with GPL were treated with either moxibustion (ST), moxibustion (Sham), or vitacoenzyme. B-cell lymphoma 2 (bcl-2), tumor protein p53 (P53) and cellular Myc (C-MYC), which are related to cell apoptosis, proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), argyrophilic nucleolar organizer region proteins (Ag-NORs), which are associated with cell proliferation, and cell signaling proteins, nuclear factor kappa B (NF-κB), epidermal growth factor receptor (EGFR) and phosphorylated extracellular signal regulated kinase (p-ERK), were measured after moxibustion treatment.Results:Compared with Control group, gastric mucosa in GPL group showed abnormal mucosal proliferation and pathological mitotic figure, the mRNA expression of bcl-2, P53 and C-MYC increased significantly (P < 0.01), the protein expression of PCNA, VEGF, Ag-NORs and the activity of NF-κβ as well as EGFR/ERK signaling proteins also increased significantly (P < 0.01). Moxibustion treatment decreased gastric mucosal proliferation and pathological mitotic figure, down-regulated the mRNA expression of bcl-2, P53, C-MYC (P < 0.01), decreased the protein expression of PCNA, VEGF, Ag-NORs and the activity of NF-κβ as well as EGFR/ERK signaling proteins significantly (P < 0.01). But moxibustion treatment of Sham didn’t show the same effect on GPL.Conclusion:Moxibustion treatment inhibited cell apoptosis and reduced gastric mucosa dysplasia by inhibiting the expression of bcl-2, P53, C-MYC and decreased the activity of NF-κβ as well as EGFR/ERK signaling proteins.

Loss of RegI in conjunction with gastrin deficiency in mice facilitates efficient gastric ulcer healing but is dispensable for hyperplasia and tumourigenesis

RegI ( Regenerating islet derived-1) was originally characterized as a growth factor involved in pancreatic islet cell regeneration. It is also considered a gastrointestinal mitogen as its expression is increased during pathologies involving aberrant cell proliferation that can lead to neoplasia. However, the absolute requirement for RegI to directly stimulate gastric mucosal cell proliferation in vivo requires further investigation. We used RegI-deficient mice to determine the requirement for RegI in normal gastric mucosal development, wound healing, hyperplasia and tumourigenesis. We found that epithelial repair of acetic acid ulcers in compound mutant RegI/gastrin-deficient mice was significantly reduced compared to wild type, RegI-deficient or gastrin-deficient mice. In contrast, RegI was dispensable for normal gastric mucosal development, hyperplasia in HKβ-deficient mice and tumourigenesis in gp130 F/F mice. Although RegI was not required for proliferation in these pathological models, expression of multiple Reg family members were increased during gp130 F/F tumourigenesis. Interestingly, loss of RegI in gp130 F/F mice resulted in decreased expression of other Reg family members. Our results indicate that RegI and gastrin may synergistically regulate gastric mucosal proliferation during certain pathological settings like wound healing while gastric epithelial proliferation in other pathologies may require coordinated expression of multiple Reg genes.

The role of melatonin on gastric mucosal cell proliferation and telomerase activity in ageing

Despite antiproliferative effects of melatonin on cultured tumor cells, its effects on normal cells are less clear. The action of melatonin on telomerase activity in ageing of gastric mucosal tissues also is not known. In this study, we investigated the age-related changes in telomerase activity and cellular proliferation rate of gastric mucosa and the effect of melatonin. A total of 37 young (4 months old), and aged (20 months old) Wistar rats, kept under equal periods of light and dark, were divided into control [(PBS), i.p. for 21 days] and melatonin-treated (10 mg/kg melatonin, i.p. for 21 days) groups. Telomerase activity, cell proliferation rate, malondialdehyde (MDA) and glutathione (GSH) levels of the stomach were determined. Melatonin significantly inhibited the gastric mucosal proliferation rate of both young and aged rats. Telomerase activity was significantly reduced in aged rats compared to young animals. Melatonin significantly increased the telomerase activity of both young and aged rats. The MDA levels of gastric mucosa in the aged rats were significantly higher than those of the younger rats. On the contrary, the GSH levels of gastric mucosa of the aged group were significantly lower than that of the young rats. While melatonin had no effect on GSH levels of either young or aged rats, it significantly decreased the MDA levels in aged animals. In conclusion, melatonin may delay the ageing of gastric mucosa by inhibiting the replicative cellular senescence via its stimulatory effect on telomerase activity and suppressive effect on cellular proliferation and lipid peroxidation.

Helicobacter pylori-induced Changes in the Gastric Mucosa are Associated With Mitogen-activated Protein Kinase (MAPK) Activation

Gastric cancers are usually associated with and preceded by Helicobacter pylori (HP) infection, gastric atrophy, intestinal metaplasia, and dysplasia. HP infection alters cell kinetics of the gastric mucosa. Both proliferation and apoptosis are increased. Proinflammatory cytokines are responsible for some of these alterations. The mitogen-activated protein kinase (MAPK) signaling pathway has been implicated as a causative factor in these alterations based on in vitro studies. In this study, we investigated the effects of HP infection on gastric mucosal proliferation, apoptotic mechanisms, and the activation status of the MAPK signaling pathway at various stages of gastric carcinogenesis, especially intestinal metaplasia and dysplasia caused by HP infection. Stomach biopsies representing normal (n=20), HP+ (n=25), HP+ with intestinal metaplasia (n=25), HP+ with dysplasia (n=15) and gastric adenocarcinoma (n=30; 20 HP+ and 10 HP-) cases were selected. Cell proliferation was assessed by proliferating cell nuclear antigen immunostaining. Apoptosis and survival-related markers; cleaved caspase-3, and phospho-MAPK extracellular signal-regulated kinase (ERK) were detected by immunohistochemical methods. Proliferation index (proliferating cell nuclear antigen) and cleaved caspase-3 expression were higher in the HP+, HP+ with intestinal metaplasia, and HP+ with dysplasia groups than in normal controls (P<0.05). Cleaved caspase-3 activity was also high in the adenocarcinomas. Phospho-MAPK(ERK) expression was increased in the HP+, HP+ with intestinal metaplasia, HP+ with dysplasia and adenocarcinomas compared with the normal control group. Whereas HP- gastric carcinomas had a lower expression of phospho-MAPK. HP infection increases the proliferative rate of gastric foveolar cells in conjunction with an increased apoptotic rate and activation of MAPK(ERK). MAPK activation seems to be a significant and persistent event in the HP-induced neoplastic transformation.

Role of mitogen-activated protein kinases in the regulation of paraventricular nucleus to gastric ischemia-reperfusion injuries

We investigated the role in electrical stimulations of paraventricular nucleus (PVN) on gastric mucosal cells and the activity of mitogen-activated protein kinases (MAPKs) family members induced by gastric ischemia-reperfusion (GI-R). And we elucidated the molecular mechanisms of the protection of PVN from GI-R injuries. Sprague-Dawley rats were divided randomly into 4 groups: Group I, the sham-operated GI-R control group; Group II, the sham-operated electrical stimulations to PVN + sham-operated GI-R control group; Group III, the GI-R group; and Group IV, the electrical stimulations to PVN + GI-R group. In all of the experiments, the PVN was stimulated prior to the induction of GI-R. The GI-R model was established by clamping the celiac artery for 30 minutes to induce ischemia and then was released to allow reperfusion for 30 minutes, 1 hour, 3 hours and 6 hours, respectively. The gastric mucosal cellular apoptosis, proliferation, and the expression and activity of MAPKs protein were observed by immunohistochemistry and Western blotting, respectively. Compared with the GI-R group, the application of electrical stimulations in the PVN significantly depressed gastric mucosal cellular apoptosis and enhanced gastric mucosal cellular proliferation following the 30-minute, 1-hour and 3-hour intervals of reperfusion; it also promoted the activation of p-ERK during the early phase of reperfusion but inhibited the activation of p-JNK1/2 and p-p38 following the 30-minute, 1-hour and 3-hour intervals of reperfusion. The protection of PVN against GI-R injuries may attribute to the inhibition of apoptosis and the promotion of the proliferation of gastric mucosal cells during GI-R. This protective effect is mediated by activating the ERK pathway and depressing the JNK, p38 MAPK pathways of the gastric mucosal cells.

EXTRACELLULAR SIGNAL-REGULATED KINASE PATHWAYS MAY MEDIATE THE PROTECTIVE EFFECT OF ELECTRICAL STIMULATION OF THE PARAVENTRICULAR NUCLEUS AGAINST ISCHAEMIA?REPERFUSION INJURY OF THE GASTRIC MUCOSA

1. The aim of the present study was to elucidate the role of the extracellular signal-regulated kinase (ERK) pathway in mediating the effects of electrical stimulation of the paraventricular nucleus (PVN) on apoptosis and proliferation induced by gastric ischaemia-reperfusion injury (GI/RI). 2. To investigate the effects of electrical stimulation of the hypothalamic PVN on gastric mucosal apoptosis and proliferation in response to ischaemia-reperfusion (I/R), we used a GI/RI model by clamping the coeliac artery for 30 min and then reperfusing the artery for 30 min or 1, 3 or 6 h. We used immunohistochemistry and western blotting to investigate the expression, activation and distribution of ERKs and the dynamic changes in their downstream cellular factors Bcl-2 and Bax at different times subsequent to electrical stimulation of the PVN in the I/R-injured gastric mucosa. 3. Electrical stimulation of the PVN markedly attenuated GI/RI at 30 min and 1 and 3 h after reperfusion. Electrical stimulation decreased gastric mucosal apoptosis, increased gastric mucosal proliferation and promoted the expression and activation of phosphorylated (p)-ERK1/2 30 min after reperfusion. Electrical stimulation increased the expression of Bcl-2 and decreased the expression of Bax at 30 min and 1 and 3 h after reperfusion. In contrast, inhibition of ERK1/2 activity by the specific upstream mitogen-activated protein kinase kinase inhibitor PD98059 produced similar effects at 1 h after reperfusion in rats subjected to I/R with or without electrical stimulation of the PVN. Administration of PD98059 aggravated gastric mucosal injury, increased apoptosis, decreased proliferation in gastric mucosal cells, decreased the expression and activity of p-ERK1/2 and Bcl-2 expression and increased Bax expression. 4. These results indicate that the PVN protects against GI/RI and that this protection is associated with the inhibition of cellular apoptosis and the promotion of proliferation in the gastric mucosa, probably by activating the ERK pathway.

Effects of hypothalamic paraventricular nuclei on apoptosis and proliferation of gastric mucosal cells induced by ischemia/reperfusion in rats

To investigate the effects of electrical stimulation of hypothalamic paraventricular nuclei (PVN) on gastric mucosal cellular apoptosis and proliferation induced by gastric ischemia/reperfusion (I/R) injury. For different experimental purposes, stimulating electrode plantation or electrolytic destruction of the PVN was applied, then the animals' GI/R injury model was established by clamping the celiac artery for 30 min and allowing reperfusing the artery for 30 min, 1 h, 3 h or 6 h respectively. Then histological, immunohistochemistry methods were used to assess the gastric mucosal damage index, the gastric mucosal cellular apoptosis and proliferation at different times. The electrical stimulation of PVN significantly attenuated the GI/R injury at 30 min, 1 h and 3 h after reperfusion. The electrical stimulation of PVN decreased gastric mucosal apoptosis and increased gastric mucosal proliferation. The electrolytic destruction of the PVN could eliminate the protective effects of electrical stimulation of PVN on GI/R injury. These results indicated that the PVN participated in the regulation of GI/R injury as a specific area in the brain, exerting protective effects against the GI/R injury, and the protection was associated with the inhibition of cellular apoptosis and the promotion of gastric mucosal proliferation. Stimulating PVN significantly inhibits the gastric mucosal cellular apoptosis and promots gastric mucosal cellular proliferation. This may explain the protective mechanisms of electrical stimulation of PVN against GI/R injury.

Effect of duodenogastric reflux on gastric mucosal proliferation after gastric surgery.

The effect of duodenogastric reflux on cell proliferation and mucosal mass in the stomach was studied. Male Wistar rats (n = 118) were submitted to Polya partial gastrectomy, partial gastrectomy with Roux-en-Y diversion of bile, total duodenogastric reflux or handling of the stomach alone (sham operation). Following oral administration of the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine for 6 months, animals were killed 6, 9 or 12 months postoperatively and their stomachs were examined for crypt cell production rate and mucosal DNA content. Compared with shams, crypt cell production rate was more than twice as high in the gastric remnant 12 months after Polya partial gastrectomy (P less than 0.001) and median DNA content was 31 per cent greater (P = 0.05). After total duodenogastric reflux, DNA content was 62 per cent greater than in shams (P = 0.02), while Roux-en-Y diversion reduced crypt cell production rate by 65 per cent (P less than 0.001). Only Polya gastrectomy increased the number of rats developing gastric carcinomas (9 versus 2 shams; P less than 0.05). Increased mucosal cell proliferation in rats with duodenogastric reflux may help to explain the development of gastric stump cancer.

Helicobacter pylori eradication treatment modulates epithelial cell proliferation and tissue content of hepatocyte growth factor in the gastric mucosa.

Although Helicobacter pylori infection is now acknowledged as a major promoter of gastric cancer in humans, the carcinogenetic process of this effect has not been fully elucidated. Precancerous lesions such as intestinal metaplasia, enhanced proliferation of epithelial cells and elevated level of growth factors have been postulated to play a role. To analyse a relationship between gastric mucosal proliferation, mucosal content of hepatocyte growth factor and prevalence of intestinal metaplasia before and after successful H. pylori eradication therapy. We evaluated 25 H. pylori-eradicated patients. At initial endoscopic examination, two biopsy tissue samples each were obtained from the antrum and great curvature of the corpus. Tissue content of hepatocyte growth factor and neutrophil myeloperoxidase were measured using an ELISA method, and histological assessment of intestinal metaplasia (haematoxylin and eosin) and proliferating cells (Ki-67 immunostaining) was performed. The patients were treated with a 1-week course of triple therapy. At 10 months after successful eradication, biochemical and histological assessments were repeated. Among all patients (n = 25), no intestinal metaplasia was detected in the corpus mucosa, but was observed in 10 patients (40%) in the antrum. This prevalence ratio was not changed after eradication. A slight decrease in HGF content was demonstrated in both sites, but the level of antral hepatocyte growth factor was significantly decreased in patients with intestinal metaplasia but not in those without. Proliferative index (Ki-67 positive cells/epithelium) was decreased after eradication therapy in both sites. An increase in proliferative index was observed in the antrum with intestinal metaplasia compared with that without, which significantly decreased after eradication therapy. H. pylori eradication therapy in the present study afforded an inhibitory effect on epithelial cell proliferation and on the mucosal content of HGF.

TFF2/SP-deficient mice show decreased gastric proliferation, increased acid secretion, and increased susceptibility to NSAID injury

Trefoil factor family 2 (TFF2), also known as spasmolytic polypeptide, is a member of the trefoil family of peptides and is expressed primarily in the mucous neck cells of the gastric mucosa. To study the physiologic role of TFF2, we have generated TFF2-deficient mice through targeted gene disruption. Homozygous mutant mice were viable and fertile without obvious gastrointestinal abnormalities. However, quantitative measurements revealed a significant decrease in gastric mucosal thickness and in gastric mucosal proliferation rates. In addition, there was a twofold increase in activated parietal cells resulting in a twofold increase in basal and stimulated gastric acid output and an undetectable serum gastrin level. The TFF2-deficient mice also showed a significant increase in the degree of gastric ulceration after administration of indomethacin. Taken together, these results suggest a physiologic role for TFF2 to promote mucosal healing through the stimulation of proliferation and downregulation of gastric acid secretion.

TFF2/SP-deficient mice show decreased gastric proliferation, increased acid secretion, and increased susceptibility to NSAID injury

Trefoil factor family 2 (TFF2), also known as spasmolytic polypeptide, is a member of the trefoil family of peptides and is expressed primarily in the mucous neck cells of the gastric mucosa. To study the physiologic role of TFF2, we have generated TFF2-deficient mice through targeted gene disruption. Homozygous mutant mice were viable and fertile without obvious gastrointestinal abnormalities. However, quantitative measurements revealed a significant decrease in gastric mucosal thickness and in gastric mucosal proliferation rates. In addition, there was a twofold increase in activated parietal cells resulting in a twofold increase in basal and stimulated gastric acid output and an undetectable serum gastrin level. The TFF2-deficient mice also showed a significant increase in the degree of gastric ulceration after administration of indomethacin. Taken together, these results suggest a physiologic role for TFF2 to promote mucosal healing through the stimulation of proliferation and downregulation of gastric acid secretion.

Aging alters gastric mucosal responses to epidermal growth factor and transforming growth factor-alpha.

Administration of pharmacological doses of epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) in young rats stimulates gastric mucosal proliferation, but, in aged rats, the same treatment inhibits proliferation. This may be due to enhanced ligand-induced internalization of EGF receptor (EGFR). In support of this, we demonstrated that although a single injection of EGF (10 microg/kg) or TGF-alpha (5 microg/kg) in young (4-6 mo old) rats greatly increased membrane-associated EGFR tyrosine kinase activity, the same treatment slightly inhibited the enzyme activity in aged (24 mo old) rats. This treatment also produced a greater abundance of punctate cytoplasmic EGFR staining in gastric epithelium of aged rats, consistent with EGFR internalization. In vitro analyses demonstrated that exposure of isolated gastric mucosal cells from aged but not young rats to 100 pM TGF-alpha resulted in marked increases in intracellular EGFR tyrosine kinase activity and that induction of EGFR tyrosine kinase activity in mucosal membranes from aged rats occurred at doses 1,000-fold less than those required in young rats. Our data suggest that aging enhances sensitivity of the gastric mucosa to EGFR ligands. This may partly explain EGFR-mediated inhibition of gastric mucosal proliferation in aged rats.

Mice deficient in membrane bound fas ag fail to increase gastric mucosal cell apoptosis or proliferation in response to helicobacter infection

Mice deficient in membrane bound fas ag fail to increase gastric mucosal cell apoptosis or proliferation in response to helicobacter infection

Mechanism of gastric mucosal proliferation induced by gastrin.

Gastrin has a potent trophic effect on gastric fundic mucosa. When serum concentrations of gastrin are elevated, proliferation of both the progenitor cells in the glandular neck zone and enterochromaffin-like (ECL) cells in the bottom of the glands is stimulated. Because ECL cells have gastrin receptors, their proliferation is directly stimulated by gastrin. However, because the proliferation of progenitor cells cannot be directly stimulated (so far there has been no gastrin receptor demonstrated on these proliferating cells), some indirect mechanisms must be involved. Enterochromaffin-like and parietal cells are only two types of cells that have demonstrated a strong gene expression of the gastrin receptor. Furthermore, they secrete several growth factors, such as Reg protein, heparin-binding epidermal growth factor-like growth factor (HB-EGF) and amphiregulin (AR). Reg protein production by ECL cells, as well as HB-EGF and AR production by parietal cells, is stimulated by gastrin and these growth factors are potent trophic agents of progenitor cells in the neck zone of the gastric fundic mucosa. Accordingly, gastrin may stimulate the proliferation of gastric mucosal cells indirectly via these growth factors in addition to its direct trophic effect on ECL cells.

Cell proliferation in the post-surgical stomach, dietary salt, and the effect of H pylori eradication.

AIMS: To study the epithelial kinetics of the post-surgical stomach with reference to dietary salt intake and H pylori. METHODS: Endoscopic biopsies of the antrum/anastomosis and corpus were taken for...

Regenerating gene protein may mediate gastric mucosal proliferation induced by hypergastrinemia in rats

Background & Aims: Regenerating gene ( Reg) has been isolated from rat regenerating pancreatic islets, and Reg protein is mitogenic to islet cells. We have recently shown that Reg gene and Reg protein are expressed in gastric enterochromaffin-like (ECL) cells. This study aimed to clarify whether gastrin enhances Reg protein production in ECL cells and whether Reg protein is mitogenic to gastric mucosal cells. Methods: Reg gene expression in response to acute and chronic hypergastrinemia was investigated in rats. Immunohistochemical studies, Northern blotting, and in situ hybridization were performed to investigate the expression of Reg protein and Reg gene. The direct effect of gastrin on Reg gene expression was investigated using isolated ECL cells, and the trophic effect of Reg protein on cultured gastric epithelial cells was assessed by [ 3H]thymidine uptake. Results: Both chronic hypergastrinemia and short-term gastrin administration stimulated Reg gene expression and Reg protein production in fundic mucosa. Reg gene expression was also augmented in isolated ECL cells after incubation with rat gastrin. Reg protein was mitogenic to cultured rat gastric epithelial cells. Conclusions: Gastrin stimulates the production of Reg protein in gastric ECL cells, which may be involved in the gastrin-induced gastric mucosal cell growth. GASTROENTEROLOGY 1998;115:1483-1493

Reg protein production by rat enterochromaffin-like cells is a possible link between hypergastrinemia and gastric mucosal proliferation

Reg protein production by rat enterochromaffin-like cells is a possible link between hypergastrinemia and gastric mucosal proliferation

The Inhibiting Effect of Cola on Gastric Mucosal Cell Cycle Proliferation in Humans

Background: Acidic beverages may be involved in regulating the cell proliferation of the gastric mucosa. We therefore analyzed the interaction of Coca-Cola consumption and gastric mucosal proliferation by means of flow cytometry. Methods: Sixteen healthy students agreed to participate in this study. All volunteers underwent an oesophagogastroduodenoscopy after a 12-h overnight fast. Endoscopic changes in the gastric mucosa were determined quantitatively. One day later, after a 12-h overnight fast, all volunteers received standard Coca-Cola (200 ml, pH 2.6, 4°C). One hour later all volunteers again underwent oesophagogastroduodenoscopy, to measure gastric mucosal damage. During both the first and the second endoscopy at least four biopsy specimens were taken from the antrum for flow cytometric analysis. Results: The endoscopic analysis showed that there was no difference before and after Coca-Cola consumption. However, the flow cytometric analysis showed that Coca-Cola inhibited the proliferation index and the S phase. Before Coca-Cola consumption G0/G1: 60 (57-62), G2/M: 0.6 (0.2-1), S: 40 (37-42), and PI: 0.40 (0.38-0.43) and after Coca-Cola consumption G0/G1: 70 (60-73), G2/M: 1.9 (1.2-2.5), S: 28 (26-32), and PI: 0.30 (0.27-0.34) the cell population G0/G1 and G2/M phases were significantly increased (P < 0.0001, 0.0003), and the cell population S and PI phases were significantly low compared with the pre-consumption data (P < 0.0002, 0.0001). Conclusion: The cell cycle analysis reflects that Coca-Cola inhibits a crucial event in the cell cycle occurring at the G1/S border.

Helicobacter pylori lipopolysaccharide stimulates histamine release and DNA synthesis in rat enterochromaffin-like cells

BACKGROUND & AIMS: Helicobacter pylori alterations in gastric acid output and mucosal proliferation may involve the enterochromaffin-like (ECL) cell. To test whether H. pylori affects ECL cell histamine secretion and proliferation, the effect of lipopolysaccharide (LPS) on ECL cell function in vitro was investigated.METHODS: Using a rat ECL cell preparation of high purity (+/-95%), basal and stimulated histamine secretion and DNA synthesis were measured by enzyme immunoassay and bromodeoxyuridine (BrdU) uptake, respectively.RESULTS: Escherichia coli LPS (10(-12) to 10(-6) mol/L) had no effect on basal and stimulated histamine secretion at concentrations of > 10(-6) mol/L. H. pylori LPS stimulated basal and gastrin-stimulated histamine secretion. These effects were completely inhibited by somatostatin (10(- 10) mol/L) but not by the gastrin receptor antagonist L365,260 at 10(- 6) mol/L. E. coli LPS had a weak stimulatory effect on ECL cell BrdU uptake at 10(-6) mol/L but had no effect on gastrin-stimulated BrdU uptake. H. pylori LPS did not stimulate basal synthesis but significantly increased (1.5-fold) gastrin-stimulated BrdU uptake.CONCLUSIONS: H. pylori influences both ECL cell proliferation and secretion in vitro. An interaction between H. pylori LPS and ECL cells may contribute to the reported abnormalities in acid secretion and gastric pathobiology noted in H. pylori infections.(Gastroenterology 1997 Oct;113(4):1110-7)