Regulation of growth and death of gastric epithelial cells by Toll-like receptors and the mox1 gene.

豚鼠胃小窝细胞表达gp91-Phox同工酶、有丝分裂原氧化酶1(Mox1)和吞噬细胞NADPH氧化酶(p67-和p22-phoxes)的基本成分。它们自发释放超氧阴离子(&lt；O2&gt；^-)。在培养的最初2天，过氧化氢酶显著抑制胸腺嘧啶核苷的摄取。用超氧化物歧化酶和过氧化氢酶或N-乙酰半胱氨酸清除~lt；O_2和相关氧化剂，用二苯碘激活的caspase3样酶抑制Moxl氧化酶，并显著促进细胞凋亡。Caspase抑制剂z-Val-Ala-Asp-CH2F可完全阻断这种加速的细胞凋亡。MOX1衍生的活性氧是构成核因子κB(NF-κB)活化的中间产物，核转录因子-kB诱骗寡核苷酸抑制其活性可加速其自发性凋亡。这些结果表明，凹陷细胞产生的O_2和…可能在其自发性凋亡和细胞增殖的调节中起着重要作用。幽门螺杆菌(HP)脂多糖(LPS)已被证明是Mox1氧化酶的有效激活剂。在无内毒素条件下，这些细胞自发分泌约10nmol/mg蛋白/h。它们表达Toll样受体4(TLR4)mRNA，而来自I型Hp的内毒素单位/毫升或更高的内毒素，可刺激TRL4介导的转化生长因子-b激活的激酶1及其结合蛋白1的磷酸化，诱导p67-Phox，并上调~lt；O_2&gt；相反，CAG致病岛完全或部分缺失突变体的Hp-内毒素对上述事件均无促进作用。脂类A是NCTC 11637 at&gt；2.1内毒素单位/ml诱导的豚鼠胃粘膜细胞凋亡的启动效应的生物活性成分。脂多糖中的A类脂蛋白介导了这种细胞凋亡。Hp脂蛋白刺激Toll样受体4(TLR4)和磷酸化的转化生长因子-b激活的蛋白1(TAK1)、TAK1结合蛋白1和c-jun氨基末端激酶(JNK)2。结果提示，IHP脂质A型可能通过刺激PIT细胞中的TLR4级联和Mox1氧化酶，对胃粘膜的增殖和凋亡起重要的调节作用。较少

Guinea pig gastric pit cells express an isozyme of gp91-phox, mitogen oxidase 1 (Mox1) and essential components for the phogocyte NADPH oxidase (p67- and p22-phoxes). They spontaneously release superoxide anion (<O_2>^-). Catalase significantly inhibited [^3H]thymidine uptake during the initial 2 days of culture. Scavenging <O_2>^- and related oxidants by superoxide dismutase plus catalase or N-acetyl cysteine and inhibiting Moxl oxidase by diphenylene iodonium activated caspase 3-like proteases and markedly enhanced apoptosis. This accelerated apoptosis was completely blocked by a caspase inhibitor, z-Val-Ala-Asp-CH2F. Mox1-derived reactive oxygen intermediates constitutively activated nuclear factor κB (NF-κB), and inhibition of this activity by NF-kB decoy oligodeoxynucleotide accelerated their spontaneous apoptosis. These results suggest that <O_2>^- produced by the pit cell Moxl oxidase may play a crucial role in the regulation of their spontaneous apoptosis as well as cell prolif … More eration.Helicobacter pylori (Hp) lipopolysaccharide (LPS) have been shown to function as potent activators for the Mox1 oxidase. These cells spontaneously secreted about 10 nmol <O_2>^-/mg protein/h in LPS-free conditions. They expressed the Toll-like receptor 4 (TLR4) mRNA, and LPS from type I Hp at 2.1 endotoxin unit/ml or higher stimulated TRL4-mediated phosphorylations of transforming growth factor-b -activated kinase 1 and its binding protein 1, induced p67-phox, and up-regulated <O_2>^- production 10-fold. In contrast, none of these events were promoted with Hp LPS from complete or partial deletion mutants of the cag pathogenicity island. Lipid A was confirmed to be a bioactive component for the priming effects Treatment of guinea pig gastric mucosal cells with LPS from NCTC 11637 at > 2.1 endotoxin unit/ml causedapoptosis. Lipid A of the LPS mediated this apoptosis. Hp LPS stimulated the Toll-like receptor 4 (TLR4) and phosphorylated transforming growth factor-b -activated kinase 1 (TAK1), TAK1 binding protein 1, and c-Jun N-terminal kinase (JNK) 2.Our results suggest that type IHp lipid A may be a potent regulator for proliferation and apoptosis of gastric mucosa by stimulating TLR4 cascade and Mox1 oxidase in pit cells. Less