Neutrophil chemoattractant 2β regulates expression of the Reg gene in injured gastric mucosa in rats
Neutrophil chemoattractant 2β regulates expression of the Reg gene in injured gastric mucosa in rats
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DOI：
10.1053/gast.2000.20262
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发表时间：
2000-12-01
期刊：
影响因子：
29.4
通讯作者：
Kinoshita, Y
中科院分区：
文献类型：
--
作者：
Kazumori, H;Ishihara, S;Kinoshita, Y
背景与目的：regen （Reg）蛋白对胃粘膜细胞具有营养作用。我们的研究表明，在粘膜糜烂周围受损的胃粘膜愈合过程中，肠色素样细胞（ECL）中的Reg基因表达增加。本研究旨在探讨胃粘膜损伤愈合过程中Reg表达的刺激物。方法：观察大鼠胃粘膜病变诱导后各种促炎因子及Reg基因表达的时间变化。利用体外逆流富集的大鼠ECL细胞，研究了促炎因子对Reg基因表达和Reg蛋白产生的直接影响。采用逆转录聚合酶链反应研究CXC受体2 （CXCR-2）在ECL细胞中的表达。在细胞因子诱导的中性粒细胞趋化剂（cinc2 β）中和抗体处理的大鼠中，也研究了regg基因的表达。结果：愈合过程中，几种促炎细胞因子及Reg基因表达明显增强。在促炎因子中，CINC-2 β是唯一一个表达增强先于Reg基因表达增加的细胞因子。用cnc -2 β中和抗体处理大鼠，可明显抑制Reg基因表达的增强。当ECL细胞与这些促炎细胞因子一起孵育时，cinc2 β剂量依赖性地增加了ECL细胞中的Reg信使RNA和Reg蛋白。在离体ECL细胞中鉴定到CXCR-2。结论：cinc2 β在受损胃黏膜中表达，通过CXCR-2刺激ECL细胞产生Reg蛋白，可能参与了损伤胃黏膜的加速愈合。
Background & Aims: Regenerating (Reg) protein has a trophic effect on gastric mucosal cells. We have shown that Reg gene expression is increased in enterochromaffin-like (ECL) cells during the healing of damaged gastric mucosa around mucosal erosion. This study was designed to explore the stimulants of Reg expression during the healing of gastric mucosal damage. Methods: Time course changes of the expression of genes for various proinflammatory cytokines and Reg were investigated after induction of gastric mucosal lesions in rats. The direct effect of proinflammatory cytokines on Reg gene expression and Reg protein production were investigated in vitro using counterflow elutriation-enriched rat ECL cells. CXC receptor 2 (CXCR-2) expression was investigated in ECL cells by reverse-transcription polymerase chain reaction. Reg gene expression was also investigated in rats treated by the neutralizing antibody of cytokine-induced neutrophil chemoattractant (CINC-2 beta). Results: During healing, the gene expression of several proinflammatory cytokines and Reg was markedly augmented. Among the proinflammatory cytokines, CINC-2 beta is the only cytokine in which augmented expression preceded the increase of Reg gene expression. In rats treated with CINC-2 beta neutralizing antibody, the augmentation of Reg gene expression was significantly inhibited. When ECL cells were incubated with these proinflammatory cytokines, CINC-2 beta dose-dependently increased Reg messenger RNA and Reg protein in ECL cells. CXCR-2 was identified in isolated ECL cells. Conclusions: CINC-2 beta, expressed in damaged gastric mucosa, stimulates the production of Reg protein in ECL cells via CXCR-2 and may be involved in the accelerated healing of injured gastric mucosa.