Interleukin 18 accelerates the hepatic cell proliferation in rat liver regeneration after partial hepatectomy

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• 作者：Jihong Zhang ; Chengkai Ma ; Yunqing Liu ; Gang Yang ; Yun Jiang ; Cunshuan Xu
• 关键词：BrdU ; bromodeoxyuridine ; DAPI ; 4&prime ; 6&prime ; -diamidino-2-phenylindole dihydrochloride ; EDTA ; ethylene diamine tetraacetic acid ; ELISA ; enzyme-linked immuno-sorbent assay ; IGIF ; interferon-纬-inducing factor ; IL-18 ; interleukin 18 ; IL-18R ; interleukin 18 receptor ; IPA ; Ingenuity Pathway Analysis ; LR ; liver regeneration ; PH ; partial hepatectomy ; rrIL-18 ; recombinant rat interleukin 18 ; RT-PCR ; real-time polymerase chain reaction ; SO ; sham operation
• 刊名：Gene
• 出版年：10 March, 2014
• 年：2014
• 卷：537
• 期：2
• 页码：230-237
• 全文大小：1190 K

文摘

Interleukin 18 (IL-18) is a proinflammatory cytokine with an ability to accelerate cell proliferation through activating other factors. However, little is yet understood of the role of IL-18 in the regulation of liver regeneration (LR). To study the effect of IL-18 on LR, the gene expression profiles of hepatocytes isolated from rat regenerative liver were determined by Rat Genome 230 2.0 microarray. Next, the synergistic effects of genes associated to IL-18 pathway were analyzed by expression profile function Et. Then, the expression level of IL-18 was examined by RT-PCR and ELISA. Finally, the effect of IL-18 on hepatocyte proliferation was detected by injecting recombinant rat IL-18 (rrIL-18) into rats immediately after partial hepatectomy (PH) and the rate of hepatocyte proliferation was detected by BrdU labeling. The microarray result showed that the expressions of 13 genes of IL-18 pathway and 49 cell proliferation genes regulated by the pathway were significantly altered at transcriptional level. The Et values of three branches of IL-18 pathway, NF-魏B, p38 and JNK, were markedly enhanced during the priming and progressing phases of rat LR. The mRNA level of IL-18 was significantly elevated at 2 and 36 h, and its level in plasma was also significantly increased at 2 h, and reached the peaks at 12 h and 48 h after PH (p < 0.05). The number of BrdU positive cells was dramatically increased in rats treated with IL-18 compared to PBS control group (p < 0.01). In conclusion, IL-18 promotes rat hepatocyte proliferation in the LR priming and progressing phases after PH.