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

Background: CXC chemokines such as interleukin (IL)-8 are neutrophil chemoa ttractants, the levels of which increase in Helicobacter pylori-infected ga stric mucosa. Many investigators have focused on the chemotactic aspects of IL-8; however, CXC chemokines are also reported to have angiogenic activit y and to serve as remodelling factors. Rat GRO/CINC-1 is a rodent counterpa rt of human GRO alpha, a member of the family of CXC chemokines. Gastric mu cosa infected with H. pylori is in a state of hyperproliferation, with incr eases in the amounts of growth factors such as hepatocyte growth factor (HG F). Aim: To investigate whether rat GRO/CINC1 had growth-stimulating activity f or 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/CI NC-1 was then added for 24 h. The total cell number was determined by fluor ogenic analysis after propidium iodide staining, and cell proliferation was assessed by measuring 5-bromo-2'-deoxyuridine (BrdU) incorporation, The ac tivity of p42/p44 mitogen-activated protein kinase (MAPK) was measured 5-20 min after the start of GRO/CINC1 exposure. Results: Cultures treated with GRO/CINC-1 showed a significant increase in cell number and BrdU incorporation in a concentration-dependent fashion. Th e MAPK activity increased within 5 min after GRO/ CINC-1 application and re turned to the control level at 20 min. Conclusion: The growth-stimulatory effect of GRO/CINC1 on rat gastric epith elial cells suggests a dual function of this chemokine: proinflammatory act ion and induction of epithelial proliferation.