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

Gastroenterology. 1996 Jan;110(1):147-54. doi: 10.1053/gast.1996.v110.pm8536851.

Abstract

Background & 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) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytokines / pharmacology*
  • Gastrins / metabolism*
  • Humans
  • Immunohistochemistry
  • Inflammation Mediators / pharmacology*
  • Interleukin-1 / pharmacology
  • Male
  • Pyloric Antrum / cytology
  • Pyloric Antrum / metabolism*
  • Rabbits
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Receptors, Tumor Necrosis Factor / antagonists & inhibitors
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Cytokines
  • Gastrins
  • Inflammation Mediators
  • Interleukin-1
  • Receptors, Interleukin-1
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha