title: Interleukin 18 accelerates the hepatic cell proliferation in rat liver regeneration after partial hepatectomy.
abstract: 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.
authors.affiliation: College of Life Science, Henan Normal University, Xinxiang 453007, Henan Province, China; Key Laboratory for Cell Differentiation Regulation, Xinxiang 453007, Henan Province, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Life Science, Henan Normal University, Xinxiang 453007, Henan Province, China; Key Laboratory for Cell Differentiation Regulation, Xinxiang 453007, Henan Province, China.
authors.forename: Chengkai
authors.initials: C
authors.lastname: Ma
authors.affiliation: College of Life Science, Henan Normal University, Xinxiang 453007, Henan Province, China; Key Laboratory for Cell Differentiation Regulation, Xinxiang 453007, Henan Province, China.
authors.forename: Yunqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Life Science, Henan Normal University, Xinxiang 453007, Henan Province, China; Key Laboratory for Cell Differentiation Regulation, Xinxiang 453007, Henan Province, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Key Laboratory for Cell Differentiation Regulation, Xinxiang 453007, Henan Province, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: College of Life Science, Henan Normal University, Xinxiang 453007, Henan Province, China; Key Laboratory for Cell Differentiation Regulation, Xinxiang 453007, Henan Province, China. Electronic address: cellkeylab@126.com.
authors.forename: Cunshuan
authors.initials: C
authors.lastname: Xu
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006498:Hepatectomy / Q000379:methods; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology; D020382:Interleukin-18 / Q000097:blood / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D020382:Interleukin-18; D016328:NF-kappa B; D011994:Recombinant Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: 4′6′-diamidino-2-phenylindole dihydrochloride; BrdU; DAPI; EDTA; ELISA; Gene expression profile; Hepatocyte proliferation; IGIF; IL-18; IL-18R; IPA; Ingenuity Pathway Analysis; Interleukin-18; LR; Liver regeneration; PH; RT-PCR; SO; bromodeoxyuridine; enzyme-linked immuno-sorbent assay; ethylene diamine tetraacetic acid; interferon-γ-inducing factor; interleukin 18; interleukin 18 receptor; liver regeneration; partial hepatectomy; real-time polymerase chain reaction; recombinant rat interleukin 18; rrIL-18; sham operation