Helicobacter felis-induced gastritis was suppressed in mice overexpressing thioredoxin-1
Helicobacter felis-induced gastritis was suppressed in mice overexpressing thioredoxin-1
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DOI：
10.1038/labinvest.3700305
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发表时间：
2005-09-01
影响因子：
5
通讯作者：
Chiba, T
中科院分区：
文献类型：
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作者：
Kawasaki, K;Nishio, A;Chiba, T
硫氧还蛋白-1（TRX-1）是一种氧化还原活性蛋白，参与清除活性氧和调节氧化还原敏感的转录因子。TRX-1在各种炎症条件下被诱导并显示细胞保护作用。我们研究了TRX-1在宿主抗猫螺杆菌（H. felis）防御机制中的作用。猫）感染。过表达人TRX-1的转基因（TG）小鼠和野生型（WT）小鼠经口接种H.猫2个月后，组织学，氧化损伤，和几种细胞因子，包括巨噬细胞炎性蛋白-2（MIP-2），相当于白细胞介素（IL）-8，在胃粘膜中的基因表达进行了研究。此外，在体内和体外研究了TRX-1对氧化应激和中性粒细胞迁移的影响。H组胃粘膜增厚;猫感染的WT小鼠，但不是在感染的TRX-1-TG小鼠。组织学上，所有H.猫感染的WT小鼠发生中度至重度胃炎，而感染的TRX-1-TG小鼠胃炎的发生被显著抑制。氧化损伤标记物8-羟基-2 '-脱氧鸟苷和丙二醛在感染的WT小鼠的胃中增加，但在TRX-1-TG小鼠中没有增加。IL-1 β和肿瘤坏死因子-α基因在H.猫感染的TRX-1-TG小鼠中的表达显著低于WT小鼠。然而，MIP-2和IL-7的上调在两组之间没有差异。TRX-1抑制氧化细胞毒性和DNA损伤，并抑制体内和体外中性粒细胞迁移。目前的研究表明，TRX-1的过表达抑制H。通过抑制中性粒细胞的趋化性和减少氧化应激来治疗猫诱导的胃炎。
Thioredoxin-1 (TRX-1) is a redox-active protein involved in scavenging reactive oxygen species and regulating redox-sensitive transcription factors. TRX-1 is induced in various inflammatory conditions and shows cytoprotective action. We investigated the roles of TRX-1 in the host defense mechanism against Helicobacter felis ( H. felis) infection. Transgenic (TG) mice overexpressing human TRX-1 and wild-type (WT) mice were orally inoculated with H. felis. After 2 months, histology, oxidative damage, and gene expression of several cytokines, including macrophage inflammatory protein-2 (MIP-2), a murine equivalent to interleukin (IL)-8, in the gastric mucosa were investigated. Furthermore, the effects of TRX-1 on oxidative stress and neutrophil migration were studied both in vivo and in vitro. The gastric mucosa was thickened in H. felis-infected WT mice, but not in infected TRX-1-TG mice. Histologically, all H. felis-infected WT mice developed moderate-to-severe gastritis, whereas the development of gastritis was significantly suppressed in infected TRX-1-TG mice. Oxidative damage markers, 8-hydroxy-2'-deoxyguanosine and malondialdehyde, increased in the stomach of infected WT mice, but not TRX-1-TG mice. Upregulation of IL-1 beta and tumor necrosis factor-alpha gene expression in H. felis-infected TRX-1-TG mice was significantly lower than in WT mice. However, upregulation of MIP-2 and IL-7 was not different between the two groups. TRX-1 suppressed oxidative cytotoxicity and DNA damage, and inhibited neutrophil migration both in vivo and in vitro. The present study suggests that overexpression of TRX-1 suppresses H. felis-induced gastritis by inhibiting chemotaxis of neutrophils and reducing oxidative stress.