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

Aliment Pharmacol Ther. 2000 Apr;14 Suppl 1:94-100. doi: 10.1046/j.1365-2036.2000.014s1094.x.

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 GROalpha, 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 G0 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.

MeSH terms

  • Animals
  • Autoradiography
  • Bromodeoxyuridine
  • Cell Division / drug effects
  • Cell Line
  • Chemokines, CXC / pharmacology*
  • Epithelial Cells / physiology*
  • Gastric Mucosa / cytology*
  • Gastric Mucosa / drug effects
  • Inflammation
  • Rats

Substances

  • Chemokines, CXC
  • Bromodeoxyuridine