Interferon gamma induction of gastric mucous neck cell hypertrophy

Weiqun Kang, Sivaprakash Rathinavelu, Linda C. Samuelson, Juanita L. Merchant

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Chronic inflammation of the gastric epithelium is believed to induce mucosal changes that can eventually develop into gastric cancer. In gastrin-deficient (G-/-) mice exhibiting chronic inflammation in the hypochlorhydric stomach, we documented a prominent fundic mucous cell lineage sharing morphological similarity with preneoplastic changes reported in Helicobacter-infected mice. To study the identity and origin of this cell lineage, we screened for different gastric mucosal cell markers. The clusters of large, foamy cells stained for trefoil factor 2 (TFF2/SP), MUC6 and the lectin Griffonia Simplicifolia II (GSII), but not for the intestine-specific transcription factor Cdx2, suggested that they arise from gastric mucous neck cells. Ki67-labeled GSII-positive neck cells in Helicobacter felis-infected, but not G-/- stomachs, suggested that mucous neck cell proliferation accounted for expansion of this compartment in the H. felis model of gastritis, but not the G-/- model. Using RNase protection assays and quantitative PCR, we found that interferon gamma (IFNγ) was the most abundant proinflammatory cytokine in the G-/- stomach. We also found that this Th1 cytokine can increase the abundance of mucous neck cells, since its infusion into mice recapitulated the appearance of these cells as observed in both G-/- and H. felis-infected mice. Using the human gastric cell line NCI-N87, we showed that IFNγ induces the secretion of mucus and expression of MUC6, TFF2 and pepsinogen II, but not of pepsinogen I and intrinsic factor. In conclusion, our results demonstrate that inflammation, specifically the proinflammatory cytokine IFNγ, induced expansion of the fundic mucous neck cell compartment, which likely represents both increased mucus production and cell number.

Original languageEnglish (US)
Pages (from-to)702-715
Number of pages14
JournalLaboratory Investigation
Volume85
Issue number5
DOIs
StatePublished - May 2005
Externally publishedYes

Keywords

  • Cdx2
  • Gastric cancer
  • Griffonia simplicifolia II (GSII)
  • Helicobacter felis
  • Inflammation
  • Trefoil factor 2 (TFF2)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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