Rat CXC chemokine GRO/CINC-1 paradoxically stimulates the growth of gastric epithelial cells

H. Suzuki, M. Mori, K. Seto, F. Shibata, S. Nagahashi, C. Kawaguchi, M. Suzuki, H. Matsui, K. Watanabe, S. Miura, H. Ishii

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Abstract

Background: CXC chemokines such as interleukin (IL)-8 are neutrophil chemoattractants, the levels of which increase in Helicobacter pylori-infected gastric mucosa. Many investigators have focused on the chemotactic aspects of IL-8: however, CXC chemokines are also reported to have angiogenic activity and to serve as remodelling factors. Rat GRO/CINC-1 is a rodent counterpart of human GROα, a member of the family of CXC chemokines. Gastric mucosa infected with H. pylori is in a state of hyperproliferation, with increases in the amounts of growth factors such as hepatocyte growth factor (HGF). Aim: To investigate whether rat GRO/CINC-1 had growth-stimulating activity for gastric epithelial cells. Methods: The rat gastric epithelial cell line RGM-1 was incubated in serum-free medium for 12 h to adjust the cell cycle to the G(o) phase, and GRO/CINC-1 was then added for 24 h. The total cell number was determined by fluorogenic analysis after propidium iodide staining, and cell proliferation was assessed by measuring 5-bromo-2'-deoxyuridine (BrdU) incorporation. The activity of p42/p44 mitogen-activated protein kinase (MAPK) was measured 5-20 min after the start of GRO/CINC-1 exposure. Results: Cultures treated with GRO/CINC-1 showed a significant increase in cell number and BrdU incorporation in a concentration-dependent fashion. The MAPK activity increased within 5 min after GRO/CINC-1 application and returned to the control level at 20 min. Conclusion: The growth-stimulatory effect of GRO/CINC- 1 on rat gastric epithelial cells suggests a dual function of this chemokine: proinflammatory action and induction of epithelial proliferation.

Original languageEnglish
Pages (from-to)94-100
Number of pages7
JournalAlimentary Pharmacology and Therapeutics, Supplement
Volume14
Issue number1
Publication statusPublished - 2000 Apr 22

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ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

Cite this

Suzuki, H., Mori, M., Seto, K., Shibata, F., Nagahashi, S., Kawaguchi, C., Suzuki, M., Matsui, H., Watanabe, K., Miura, S., & Ishii, H. (2000). Rat CXC chemokine GRO/CINC-1 paradoxically stimulates the growth of gastric epithelial cells. Alimentary Pharmacology and Therapeutics, Supplement, 14(1), 94-100.