Gastrin secretion from primary cultures of rabbit antral G cells: stimulation by inflammatory cytokines.
OBJECTIVE
In Helicobacter pylori-induced gastritis, local production of cytokines may favor hypergastrinemia as an endocrine link between H. pylori-induced gastritis and duodenal ulcer. The aim of this study was to characterize cytokine effects on cultured rabbit antral G cells.


METHODS
Monolayers (14.2% +/- 2.9% G cells) were studied after 48 hours in primary culture.


RESULTS
Interleukin (IL) 1 beta (50% effective concentration [EC50], 5.3 +/- 0.4 ng/mL) and tumor necrosis factor (TNF) alpha (EC50, 5.5 +/- 0.5 ng/mL) stimulated gastrin release to 50% of the maximal response to 10(-9) mol/L neuromedin C. Stimulation by the maximally effective concentration of IL-1 beta (10 ng/mL) was inhibited by the human IL-1 receptor antagonist (100 ng/mL; inhibitory constant, 23.0 ng/mL), which prefers type I over type II IL-1 receptors. The response to the maximally effective concentration of TNF-alpha (10 ng/mL) was markedly inhibited by monoclonal antibody H398, an antagonist at TNF P55 receptors (inhibitory constant, 1.7 micrograms/mL), whereas monoclonal antibody utr1, an antagonist at TNF P75 receptors, was ineffective. Stimulation by IL-1 beta and TNF-alpha was additive to the responses to neuromedin C and O2-dibutyryl adenosine 3',5'-cyclic monophosphate. IL-6 and IL-8 (0.1-50 ng/mL) were ineffective.


CONCLUSIONS
IL-1 beta and TNF-alpha stimulate gastrin secretion via receptors potentially residing on rabbit antral G cells themselves. We speculate that G cells express type I IL-1 receptors and TNF P55 but not TNF P75 receptors.
Weigert
N
N
Second Department of Internal Medicine, Technical University of Munich, Germany.
Schaffer
K
K
Schusdziarra
V
V
Classen
M
M
Schepp
W
W
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D005755:Gastrins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D011706:Pyloric Antrum / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D005755:Gastrins; D018836:Inflammation Mediators; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha