Interleukin 18 accelerates the hepatic cell proliferation in rat liver regeneration after partial hepatectomy.
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-κB, 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 2h, and reached the peaks at 12h 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.
['Zhang|Jihong|J|', 'Ma|Chengkai|C|', 'Liu|Yunqing|Y|', 'Yang|Gang|G|', 'Jiang|Yun|Y|', 'Xu|Cunshuan|C|']
D000818:Animals D049109:Cell Proliferation D005786:Gene Expression Regulation D006498:Hepatectomy D022781:Hepatocytes D020382:Interleukin-18 D048031:JNK Mitogen-Activated Protein Kinases D008115:Liver Regeneration D008297:Male D016328:NF-kappa B D020411:Oligonucleotide Array Sequence Analysis D051381:Rats D017207:Rats, Sprague-Dawley D011994:Recombinant Proteins D015398:Signal Transduction D048051:p38 Mitogen-Activated Protein Kinases
interleukin 18 Liver regeneration Liver regeneration partial hepatectomy IL-18 LR Gene expression profile RT-PCR ELISA Hepatocyte proliferation rrIL-18 PH BrdU 4′6′-diamidino-2-phenylindole dihydrochloride DAPI EDTA IGIF IL-18R IPA Ingenuity Pathway Analysis Interleukin-18 SO bromodeoxyuridine enzyme-linked immuno-sorbent assay ethylene diamine tetraacetic acid interferon-γ-inducing factor interleukin 18 receptor liver regeneration real-time polymerase chain reaction recombinant rat interleukin 18 sham operation