Rat CXC chemokine GRO/CINC-1 paradoxically stimulates the growth of gastric epithelial cells
Rat CXC chemokine GRO/CINC-1 paradoxically stimulates the growth of gastric epithelial cells
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DOI：
10.1046/j.1365-2036.2000.014s1094.x
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发表时间：
2000-04-01
影响因子：
7.6
通讯作者：
Ishii, H
中科院分区：
文献类型：
--
作者：
Suzuki, H;Mori, M;Ishii, H
背景：CXC趋化因子如白细胞介素（IL）-8是中性粒细胞趋化因子，其水平在幽门螺杆菌感染的胃粘膜中增加。许多研究人员将注意力集中在 IL-8 的趋化作用上。然而，据报道 CXC 趋化因子也具有血管生成活性并可作为重塑因子。大鼠 GRO/CINC-1 是人类 GRO α（CXC 趋化因子家族成员）的啮齿动物对应物。感染H. pylori的胃粘膜处于过度增殖状态，肝细胞生长因子（HGF）等生长因子数量增加。目的：探讨大鼠GRO/CINC1是否对胃上皮细胞具有刺激生长活性。方法：将大鼠胃上皮细胞系RGM-1在无血清培养基中培养12 h，将细胞周期调整至G（o）期，然后加入GRO/CINC-1进行促生长。 24小时。碘化丙啶染色后通过荧光分析测定总细胞数，通过测量 5-溴-2'-脱氧尿苷 (BrdU) 掺入情况评估细胞增殖，在 GRO/CINC1 暴露开始后 5-20 分钟测量 p42/p44 丝裂原激活蛋白激酶 (MAPK) 的活性。 结果：用 GRO/CINC-1 处理的培养物显示细胞数和 BrdU 显着增加以浓度依赖性方式掺入。 GRO/CINC-1应用后5分钟内MAPK活性增加，并在20分钟时恢复到对照水平。结论：GRO/CINC1对大鼠胃上皮细胞的生长刺激作用表明该趋化因子具有双重功能：促炎作用和诱导上皮增殖。
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 GRO alpha, 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/CINC1 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/CINC1 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/CINC1 on rat gastric epithelial cells suggests a dual function of this chemokine: proinflammatory action and induction of epithelial proliferation.