title: Rat CXC chemokine GRO/CINC-1 paradoxically stimulates the growth of gastric epithelial cells.
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).
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.forename: K
authors.initials: K
authors.lastname: Seto
authors.forename: F
authors.initials: F
authors.lastname: Shibata
authors.forename: S
authors.initials: S
authors.lastname: Nagahashi
authors.forename: C
authors.initials: C
authors.lastname: Kawaguchi
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Matsui
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: S
authors.initials: S
authors.lastname: Miura
authors.forename: H
authors.initials: H
authors.lastname: Ishii
mesh_terms: D000818:Animals; D001345:Autoradiography; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D019743:Chemokines, CXC / Q000494:pharmacology*; D004847:Epithelial Cells / Q000502:physiology*; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects; D007249:Inflammation; D051381:Rats
chemical_list: D019743:Chemokines, CXC; D001973:Bromodeoxyuridine