Rat CXC chemokine GRO/CINC-1 paradoxically stimulates the growth of gastric epithelial cells.
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.
Suzuki
H
H
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Mori
M
M
Seto
K
K
Shibata
F
F
Nagahashi
S
S
Kawaguchi
C
C
Suzuki
M
M
Matsui
H
H
Watanabe
K
K
Miura
S
S
Ishii
H
H
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
D019743:Chemokines, CXC; D001973:Bromodeoxyuridine