幽门螺杆菌激活人胃上皮细胞中的蛋白激酶C，通过抑制细胞外信号调节激酶来限制白细胞介素-8的产生。

Protein kinase C activation by Helicobacter pylori in human gastric epithelial cells limits interleukin-8 production through suppression of extracellular signal-regulated kinase.

作者信息

Nozawa Yoshihisa, Nishihara Katsushi, Akizawa Yushiro, Orimoto Naoki, Nakano Motoko, Uji Tatsuya, Ajioka Hirofusa, Kanda Atsuhiro, Matsuura Naosuke, Kiniwa Mamoru

机构信息

Pharmacobioregulation Research Laboratory, Taiho Pharmaceutical Co, Ltd, Saitama, Japan.

出版信息

J Pharmacol Sci. 2004 Mar;94(3):233-9. doi: 10.1254/jphs.94.233.

DOI:10.1254/jphs.94.233

PMID:15037807

Abstract

Helicobacter pylori (H. pylori) infection of gastric epithelial cells has been shown to induce interleukin (IL)-8 production, but the signal transduction mechanism leading to IL-8 production has not been clearly defined. Here, we investigate the role of protein kinase C (PKC) in the mechanism of induction of IL-8 release by H. pylori in human gastric epithelial cells. In MKN45 cells, H. pylori-induced IL-8 release was enhanced by treatment with PKC inhibitors (GF109203X and calphostin C) and PKC depletion, which completely inhibited PKC activity. Moreover, PKC inhibitors and PKC depletion increased extracellular signal-regulated kinase (ERK) activity and phosphorylation, but not calcium/calmodulin-dependent protein kinase II (CaMK II) activity, in response to H. pylori infection. PKC activated by H. pylori inhibited activation of ERK induced by H. pylori without affecting the CaMK II activity and negatively regulated IL-8 production in human gastric epithelial cells.

摘要

幽门螺杆菌（H. pylori）感染胃上皮细胞已被证明可诱导白细胞介素（IL）-8的产生，但导致IL-8产生的信号转导机制尚未明确界定。在此，我们研究蛋白激酶C（PKC）在幽门螺杆菌诱导人胃上皮细胞释放IL-8的机制中的作用。在MKN45细胞中，用PKC抑制剂（GF109203X和钙泊三醇）处理以及PKC缺失可增强幽门螺杆菌诱导的IL-8释放，而PKC缺失完全抑制了PKC活性。此外，PKC抑制剂和PKC缺失可增加细胞外信号调节激酶（ERK）的活性和磷酸化水平，但对幽门螺杆菌感染的反应中，钙/钙调蛋白依赖性蛋白激酶II（CaMK II）的活性未增加。幽门螺杆菌激活的PKC可抑制幽门螺杆菌诱导的ERK激活，而不影响CaMK II的活性，并对人胃上皮细胞中IL-8的产生起负调节作用。