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

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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 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.