Effect of transforming growth factor alpha and interleukin 8 on somatostatin release from canine fundic D cells.
OBJECTIVE
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.
Beales
I
I
Department of Gastroenterology, Royal Postgraduate Medical School, London, England.
Calam
J
J
Post
L
L
Srinivasan
S
S
Yamada
T
T
DelValle
J
J
D000818:Animals; D002478:Cells, Cultured; D004285:Dogs; D005748:Gastric Fundus / Q000187:drug effects* / Q000378:metabolism; D016209:Interleukin-8 / Q000494:pharmacology*; D013004:Somatostatin / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D016209:Interleukin-8; D016211:Transforming Growth Factor alpha; D013004:Somatostatin