Effect of interlukin-1beta on proliferation of gastric epithelial cells in culture.
Effect of interlukin-1beta on proliferation of gastric epithelial cells in culture.
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DOI：
10.1186/1471-230x-2-7
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发表时间：
2002-04-05
影响因子：
2.4
通讯作者：
Beales IL
中科院分区：
文献类型：
--
作者：
Beales IL
幽门螺杆菌是非贲门部胃癌发生的主要危险因素。胃粘膜增生增加是H.幽门感染在H. pylori感染和IL-1β基因型与促炎活性增加相关是胃癌发生的危险因素。本研究探讨了IL-1β对胃上皮细胞增殖的影响。AGS细胞与IL-1β共同培养。[3 H]胸腺嘧啶核苷掺入法测定细胞DNA合成，MTT法测定总活细胞数。IL-1β剂量依赖性地增加DNA合成和细胞数量。IL-1受体拮抗剂可阻断细胞增殖。向GM-CSF中加入中和抗体可使IL-1β刺激的增殖降低31 ± 4%。单独的GM-CSF显著刺激增殖。添加或中和IL-8对基础或IL-1β刺激的增殖无影响。酪氨酸激酶抑制剂genistein完全阻断IL-1β刺激的增殖，并且用PD 98059抑制细胞外信号相关激酶途径使IL-1β刺激的增殖抑制58 ± 5%。IL-1β刺激胃上皮细胞增殖。GM-CSF的自分泌刺激有助于这种增殖反应。通过酪氨酸激酶活性的信号传导对于对IL-1β的促有丝分裂应答是必需的。细胞外信号相关激酶途径参与下游信号传导，但不是必需的。IL-1β可能参与了H.幽门螺杆菌感染的胃粘膜，并参与致癌过程。
Helicobacter pylori is the main risk factor for the development of non-cardia gastric cancer. Increased proliferation of the gastric mucosa is a feature of H. pylori infection. Mucosal interkeukin-1β production is increased in H. pylori infection and IL-1β genotypes associated with increased pro-inflammatory activity are risk factors for the development of gastric cancer. The effect of IL-1β on gastric epithelial cell proliferation has been examined in this study. AGS cells were cultured with IL-1β. DNA synthesis was assed by [3H]thymidine incorporation and total viable cell numbers by MTT assay. IL-1β dose dependently increased DNA synthesis and cell numbers. The enhanced proliferation was blocked by interleukin-1 receptor antagonist. Addition of neutralising antibody to GM-CSF reduced IL-1β-stimulated proliferation by 31 ± 4 %. GM-CSF alone significantly stimulated proliferation. Addition or neutralisation of IL-8 had no effect on basal or IL-1β-stimulated proliferation. The tyrosine kinase inhibitor genistein completely blocked IL-1β-stimulated proliferation and inhibition of the extracellular signal related kinase pathway with PD 98059 inhibited IL-1β stimulated proliferation by 58 ± 5 %. IL-1β stimulates proliferation in gastric epithelial cells. Autocrine stimulation by GM-CSF contributes to this proliferative response. Signalling via tyrosine kinase activity is essential to the mitogenic response to IL-1β. The extracellular signal related kinase pathway is involved in, but not essential to downstream signalling. IL-1β may contribute to the hyperproliferation seen in H. pylori- infected gastric mucosa, and be involved in the carcinogenic process.