TY - JOUR
T1 - Interferon gamma induction of gastric mucous neck cell hypertrophy
AU - Kang, Weiqun
AU - Rathinavelu, Sivaprakash
AU - Samuelson, Linda C.
AU - Merchant, Juanita L.
N1 - Funding Information:
This work was supported by the Public Health Service Grants R01 DK61410 to JLM, and the Cell Biology Core of P01DK62401 to JLM. We express our appreciation to Drs Yana Zavros and Longchuan Bai, and Ms Judy Poore of the Cell Biology Michigan DDRC Center (P30DK34933), for invaluable technical assistance. We also thank Kathy McClinchey (McClinchey Histology Lab, Inc., Stockbridge, MI, USA) for paraffin embedding and sectioning fixed tissues.
PY - 2005/5
Y1 - 2005/5
N2 - 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.
AB - 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.
KW - Cdx2
KW - Gastric cancer
KW - Griffonia simplicifolia II (GSII)
KW - Helicobacter felis
KW - Inflammation
KW - Trefoil factor 2 (TFF2)
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U2 - 10.1038/labinvest.3700260
DO - 10.1038/labinvest.3700260
M3 - Article
C2 - 15765119
AN - SCOPUS:18744409088
SN - 0023-6837
VL - 85
SP - 702
EP - 715
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 5
ER -