Ding S Z, Cho C H, Lam S K
Department of Medicine, University of Hong Kong, China.
Biochem Biophys Res Commun. 1997 Nov 26;240(3):561-5. doi: 10.1006/bbrc.1997.7699.
Helicobacter pylori (HP) infection has been shown to increase gastric mucosal interleukin 8 (IL-8) expression, and whether HP or its toxin induces endothelial cell IL-8 expression is unknown. We aimed to compare the IL-8 expression in endothelial cells after stimulation with HP toxin, tumor necrosis factor alpha (TNF-alpha), and lipopolysaccharide (LPS) and to study their signal pathways. HP or its toxin induced significant IL-8 expression in endothelial cells. HP toxin, TNF-alpha, and LPS also showed a time- and dose-dependent increase in IL-8 expression over the control. Both protein kinase C (PKC) and protein kinase A (PKA) inhibitors had no effect on IL-8 response to these stimuli. Protein tyrosine kinase (PTK) inhibitor genistein at concentrations of 150, 300, and 450 microM dose-dependently reduced LPS- and TNF-alpha-induced IL-8 expression by 29.43, 43.8, and 47.3% and 20.5, 49.9, and 61.8% respectively, whereas HP toxin-induced IL-8 secretion could only be reduced at 450 microM by 35.7%. Geldanamycin, a more potent PTK inhibitor, at doses of 0.5, 1, and 2 microM dose-dependently reduced HP toxin induced endothelial cell IL-8 expression by 24.8, 26, and 44.3% respectively. It is concluded that HP and its toxin can increase IL-8 expression in endothelial cells, and the expression of IL-8 elicited by HP toxin, TNF-alpha, and LPS is partially dependent on PTK but not PKA or PKC activation.
幽门螺杆菌（HP）感染已被证明会增加胃黏膜白细胞介素8（IL-8）的表达，而HP或其毒素是否会诱导内皮细胞IL-8表达尚不清楚。我们旨在比较用HP毒素、肿瘤坏死因子α（TNF-α）和脂多糖（LPS）刺激后内皮细胞中IL-8的表达，并研究它们的信号通路。HP或其毒素可诱导内皮细胞中显著的IL-8表达。与对照组相比，HP毒素、TNF-α和LPS还显示出IL-8表达呈时间和剂量依赖性增加。蛋白激酶C（PKC）和蛋白激酶A（PKA）抑制剂对这些刺激引起的IL-8反应均无影响。浓度为150、300和450微摩尔的蛋白酪氨酸激酶（PTK）抑制剂染料木黄酮分别剂量依赖性地降低LPS和TNF-α诱导的IL-8表达29.43%、43.8%和47.3%以及20.5%、49.9%和61.8%，而HP毒素诱导的IL-8分泌仅在450微摩尔时可降低35.7%。更有效的PTK抑制剂格尔德霉素，剂量为0.5、1和2微摩尔时，分别剂量依赖性地降低HP毒素诱导的内皮细胞IL-8表达24.8%、26%和44.3%。结论是，HP及其毒素可增加内皮细胞中IL-8的表达，HP毒素、TNF-α和LPS诱导的IL-8表达部分依赖于PTK，但不依赖于PKA或PKC的激活。
