Interferon-γ modulates cAMP-induced mucin exocytosis without affecting mucin gene expression in a human colonic goblet cell line

Anne Jarry, Didier Merlin, Anna Velcich, Ulrich Hopfer, Leonard H. Augenlicht, Christian L. Laboisse

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29 Scopus citations

Abstract

The regulation of intestinal mucin secretion by cytokines, soluble factors released by mucosal activated immune cells, is so far unknown. The aim of the present study was (1) to investigate the regulatory effects of interferon-γ on baseline and stimulated mucin secretion elicited by an increase in intracellular cAMP, either a short-term increase (induced by vasoactive intestinal peptide or by forskolin) or a long-term increase (cholera toxin-induced), and (2) to attempt to delineate the site of action of interferon-γ. The in vitro model used was the human colonic goblet cell line C1.16E, which has already been shown to respond to physiological secretagogues in terms of mucin secretion. We examined the effects of interferon-γ 1) on mucin exocytosis, measured as release of [3H]glucosamine-labeled macromolecules trapped at the stacking/running gel interface of polyacrylamide gels, and 2) on mucin biosynthesis, examined at the RNA level using a cDNA probe directed to the MUC2 mucin gene. We demonstrated that, while interferon-γ did not alter baseline Cl.16E mucin secretion and MUC2 gene expression, it strongly inhibited the protein kinase A-dependent secretory response to VIP, forskolin, or cholera toxin. However, interferon-γ had no effect on the protein kinase A-dependent MUC2 over-expression induced by cholera toxin. We thus concluded that the target for interferon-γ inhibition of cAMP-stimulated Cl.16E mucin secretion is distal to protein kinase A and might be a component of the exocytotic machinery. Together, our results establish interferon-γ as a pharmacologically powerful tool to specifically inhibit stimulated secretory processes without affecting baseline secretion.

Original languageEnglish (US)
Pages (from-to)95-103
Number of pages9
JournalEuropean Journal of Pharmacology: Molecular Pharmacology
Volume267
Issue number1
DOIs
Publication statusPublished - Mar 15 1994

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Keywords

  • Colonic cell line (Human)
  • Cytokine regulation
  • Interferon-γ, cAMP
  • MUC2 mucin gene
  • Mucus secretion

ASJC Scopus subject areas

  • Pharmacology

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