TY - JOUR
T1 - Rat CXC chemokine GRO/CINC-1 paradoxically stimulates the growth of gastric epithelial cells
AU - Suzuki, H.
AU - Mori, M.
AU - Seto, K.
AU - Shibata, F.
AU - Nagahashi, S.
AU - Kawaguchi, C.
AU - Suzuki, M.
AU - Matsui, H.
AU - Watanabe, K.
AU - Miura, S.
AU - Ishii, H.
PY - 2000
Y1 - 2000
N2 - 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 G(o) 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.
AB - 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 G(o) 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.
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U2 - 10.1046/j.1365-2036.2000.014s1094.x
DO - 10.1046/j.1365-2036.2000.014s1094.x
M3 - Article
C2 - 10807410
AN - SCOPUS:0034032986
SN - 0953-0673
VL - 14
SP - 94
EP - 100
JO - Alimentary Pharmacology and Therapeutics, Supplement
JF - Alimentary Pharmacology and Therapeutics, Supplement
IS - 1
ER -