Gastrin secretion from primary cultures of rabbit antral G cells: Stimulation by inflammatory cytokines

Abstract

Background and Aims: 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) 1β (50% effective concentration [EC50], 5.3 ± 0.4 ng/mL) and tumor necrosis factor (TNF) α (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-1β (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-α (10 ng/mL) was markedly inhibited by monoclonal antibody H398, an antagonist at TNF P55 receptors (inhibitory constant, 1.7 μg/mL), whereas monoclonal antibody utr1, an antagonist at TNF P75 receptors, was ineffective. Stimulation by IL-1β and TNF-α 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-1β and TNF-α 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.