Effect of transforming growth factor alpha and interleukin 8 on somatostatin release from canine fundic D cells

doi:10.1016/S0016-5085(97)70228-2

Gastroenterology

Volume 112, Issue 1, January 1997, Pages 136-143

https://doi.org/10.1016/S0016-5085(97)70228-2 Get rights and content

Abstract

BACKGROUND & AIMS: Helicobacter pylori infection in patients who have peptic ulcer disease is associated with altered regulation of gastric secretion, hypergastrinemia, and diminished somatostatin expression in gastric mucosa. Tumor necrosis factor (TNF)-alpha and interleukin (IL)- 8 are the predominant cytokines produced in the gastric mucosa of patients with H. pylori infection. The aim of this study was to examine whether IL-8 and TNF-alpha could regulate somatostatin release from isolated canine gastric D cells. METHODS: Canine gastric D cells were isolated from fundic mucosa and enriched by centrifugal elutriation. Secretagogue-stimulated somatostatin release was measured by radioimmunoassay. RESULTS: TNF-alpha dose dependently increased somatostatin release after 2 hours of treatment. The stimulatory effect of TNF-alpha was additive to that of epinephrine but was unaffected by a maximal concentration of cholecystokinin. IL-8 did not alter basal or secretagogue (cholecystokinin, epinephrine)-mediated somatostatin release. The stimulatory effect of TNF-alpha (10 ng/mL) was potentiated by the addition of IL-8 (1 nmol/L), inhibited by octreotide and staurosporine, but unaffected by indomethacin. Pretreatment of D cells with TNF-alpha (10 ng/mL) for 24 hours abolished the subsequent stimulatory effect of this cytokine and secretagogues on somatostatin release. CONCLUSIONS: TNF-alpha was shown to regulate somatostatin release from cultured D cells in a divergent manner. (Gastroenterology 1997 Jan;112(1):136-43)

References (0)

Cited by (60)

Immunology of Helicobacter pylori: Insights Into the Failure of the Immune Response and Perspectives on Vaccine Studies
2007, Gastroenterology
Citation Excerpt :
In H pylori infection this negative feedback mechanism is disrupted.128,147 The Th1 immunoregulatory cytokine IFN-γ141 and TNF-α148 inhibit somatostatin secretion by D cells. In contrast, administration of the Th2 cytokine IL-4 in mice stimulates increased gastric somatostatin concentrations and suppresses gastrin secretion.141
Helicobacter pylori infects the stomach of half of the human population worldwide and causes chronic active gastritis, which can lead to peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. The host immune response to the infection is ineffective, because the bacterium persists and the inflammation continues for decades. Bacterial activation of epithelial cells, dendritic cells, monocytes, macrophages, and neutrophils leads to a T helper cell 1 type of adaptive response, but this remains inadequate. The host inflammatory response has a key functional role in disrupting acid homeostasis, which impacts directly on the colonization patterns of H pylori and thus the extent of gastritis. Many potential mechanisms for the failure of the host response have been postulated, and these include apoptosis of epithelial cells and macrophages, inadequate effector functions of macrophages and dendritic cells, VacA inhibition of T-cell function, and suppressive effects of regulatory T cells. Because of the extent of the disease burden, many strategies for prophylactic or therapeutic vaccines have been investigated. The goal of enhancing the host’s ability to generate protective immunity has met with some success in animal models, but the efficacy of potential vaccines in humans remains to be demonstrated. Aspects of H pylori immunopathogenesis are reviewed and perspectives on the failure of the host immune response are discussed. Understanding the mechanisms of immune evasion could lead to new opportunities for enhancing eradication and prevention of infection and associated disease.
Helicobacter pylori and benign upper digestive disease
2007, Best Practice and Research in Clinical Gastroenterology
Citation Excerpt :
Suppression by somatostatin may be the initial step of the whole cascade.47 Proinflammatory cytokines like tumour necrosis factor alpha (TNFα) and interleukin-8 interfere the release of gastrin and somatostatin.48–50 However, hypergastrinaemia does not always lead to duodenal ulcers.
Acute infection with Helicobacter pylori causes hypochlorhydria and gastrointestinal upset. As the infection persists, patients develop chronic antral-predominant or pangastritis. Gastric and duodenal ulcers arise from chronic mucosal inflammation and disordered acid secretion in the stomach. With successful eradication of H. pylori, non-NSAID-related gastric and duodenal ulcers heal even without long-term acid suppression. More importantly, peptic ulcers and their complications rarely recur. Clearing H. pylori infection also reduces the risk of mucosal injury in NSAID and aspirin users; the protective effects are more pronounced in NSAID-naïve and aspirin users. H. pylori is unlikely to be the cause of gastro-oesophageal reflux disease. However, a patient's reflux symptoms may be more difficult to control after clearing the infection. Although there is little evidence to support a causal relationship between H. pylori and non-ulcer dyspepsia, treatment of the infection gives a modest improvement of symptoms.
Modulating the cytokine response to treat Helicobacter gastritis
2005, Biochemical Pharmacology
The conventional view of gastric acid secretion is that a negative feedback mechanism arises in response to high acidity, such that somatostatin keeps G-cells and parietal cells from producing more gastrin and acid, respectively. When the stomach becomes infected, for example with Helicobacter pylori (H. pylori), the feedback mechanism is impaired. In animal models, our laboratory has demonstrated that other types of bacteria besides H. pylori can cause gastritis. For example, under conditions of low acidity, gastritis is secondary to bacterial overgrowth, not production of excessive acid, thus suggesting a new paradigm for the regulation of gastric acid secretion under inflammatory conditions. Cytokines, released during the gastric inflammatory response, including IFNγ, TNFα and IL-1β stimulate the G-cell to produce gastrin. Gastrin in turn triggers the release of acid, and hypergastrinemia suppresses somatostatin, the inhibitor of acid. The overall response results in maximal gastric acid output that acts as the stomach's most important anti-microbial agent. The increased acid secretion by the stomach in the presence of H. pylori seems to be part of the innate immune response, in that gastrin and somatostatin are reciprocally regulated by Th1 or Th2 cytokines, respectively. In a mouse model, we showed that octreotide, a somatostatin, analog, is an efficacious treatment for Helicobacter gastritis. In humans, octreotide might accelerate recovery from H. pylori infection, reducing the duration of antibiotic therapy.
Persistent decreased plasma cholecystokinin levels in celiac patients under gluten-free diet: Respective roles of histological changes and nutrient hydrolysis
2002, Regulatory Peptides
Celiac disease is associated with impaired cholecystokinin (CCK) release. The mechanism by which CCK release is impaired is poorly understood and seems to be related to the mucosal atrophy or to decreased stimulation due to reduced intraduodenal nutrient hydrolysis. The aims of our study were to evaluate basal and postprandial CCK in celiac patients presenting with distinctive types of mucosal lesions (normal, infiltrative and atrophic), and to study the role of protein hydrolysis on CCK release. Plasma CCK was measured in 20 celiac patients (normal mucosa: n=6; infiltrative type: n=6; atrophic type=8) and 9 controls, before and after ingestion of a polymeric or a semi-elemental meal. Significant decreases in basal CCK plasma (B 0.6 [95% CI, 0.3–1.3] pmol/l; p<0.003) and postprandial CCK area under curve (AUC 34 [19–61] pmol/l×120 min, p<0.0001) were observed in patients with an atrophic mucosa compared with treated patients (B 1.6 [1.0–2.4] pmol/l, AUC 267 [172–414] pmol/l×120 min) or healthy volunteers (B 1.0 [0.7–1.4] pmol/l, AUC 186 [131–264] pmol/l×120 min). A significant defective CCK release was also observed in patients with an infiltrative type: B 0.4 [0.2–0.7] pmol/l and AUC 56 [31–101] pmol/l×120 min; p<0.0001. Administration of a semi-elemental diet did not correct the defective CCK release. In conclusion, the decreased CCK levels observed in celiac patients are not strictly related to the mucosal atrophy but rather to the lymphocytic infiltrate. Administration of a predigested meal did not correct the impaired CCK release. Some inhibitory mechanism could be involved in the CCK cell dysfunction observed in celiac patients presenting with lesser degrees of disease activity.
Peptic-ulcer disease
2002, Lancet
Citation Excerpt :
Alternatively, H pylori-associated antral gastritis might affect D cells and G cells by stimulating the production of cytokines. Results from recent in-vitro studies show that some proinflammatory cytokines, such as interleukin-8 and TNF-α, affect the release of somatostatin and gastrin.15,16 The net result of these effects is an increase in acid production, and hence duodenal acid load.
The discovery of Hellcobacter pylori has greatly changed our approach to peptic ulcer disease. Bacterial, host, and environmental factors all have a role in peptic-ulcer disease. Although the prevalence of uncomplicated peptic ulcers is falling, hospital admissions for ulcer complications associated with non-steroidal anti-inflammatory drugs (NSAIDs) are rising. Evidence suggests that coprescription of NSAIDs with potent antiulcer agents and the use of highly selective cyclo-oxygenase-2 inhibitors reduce gastroduodenal ulceration. Whether these therapeutic advances will translate into clinical benefits remains to be seen. The interaction between H pylori and NSAIDs is one of the most controversial issues in peptic ulcer disease. With the fall in rates of H pylori infection, the proportion of ulcers not related to this organism and NSAIDs has risen, which will affect the management of peptic ulcer.
Monoclonal antibody to tumor necrosis factor-α reduces hypergastrinemia in Helicobacter pylori infection [1]
2001, American Journal of Medicine

View all citing articles on Scopus

View full text