title: Gene expression profile analysis of the mouse liver during bacteria-induced fulminant hepatitis by a cDNA microarray system.
abstract: Fulminant hepatic failure (FHF) is a disease characterized by sudden and severe impairment of liver function. To elucidate the mechanism involved in FHF, we adopted a murine model of FHF by administrating mice with heat-killed Propionibacterium acnes (P. acnes), followed by a low dose of lipopolysaccharide (LPS), and analyzed the dynamic change of gene expression profile of the murine liver using an in-house cDNA microarray system which contained most of the cDNAs encoding chemokines/cytokines and their receptors (33 chemokines/21 chemokine receptors, 28 cytokines/35 cytokine receptors) as well as 230 liver related proteins mostly selected by serial analysis of gene expression (SAGE). Among them, 335 genes were found to differ by more than 2-fold in at least one time point comparing with normal liver. Hierarchical cluster analysis revealed that except for a few genes, such as heme oxygenase (HO)-1 and nicotinamide N-methyltransferase (NNMT) of which expression increased, the expression of most of the genes encoding drug metabolizing enzymes decreased with the progress of the disease. The expression of the genes encoding chemokines/cytokines was dramatically changed, such as Mig, IP-10, RANTES, TNF-alpha, and IFN-gamma. In addition, the expression of those that were not previously linked to this murine model was also identified to be changed. These include endogenous IL-18 binding protein (IL-18BP), CXCL16 (the ligand of Bonzo, CXCR6) as well as ESTs. Taken together this study has shown the systemic and comprehensive gene expression profile during FHF and may contribute to better understanding of the mechanism of FHF.
authors.affiliation: Department of Molecular Preventive Medicine & CREST, School of Medicine, The University of Tokyo, Japan.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Dong
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Toyoda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoneyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Kurachi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kasahara
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Hidekuni
authors.initials: H
authors.lastname: Inadera
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D020224:Expressed Sequence Tags; D005260:Female; D020869:Gene Expression Profiling; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D051547:Heme Oxygenase-1; D006520:Hepatitis, Animal / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D017093:Liver Failure / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins; D008780:Methyltransferases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D050903:Nicotinamide N-Methyltransferase; D020411:Oligonucleotide Array Sequence Analysis; D011425:Propionibacterium acnes / Q000472:pathogenicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics; D018121:Receptors, Cytokine / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D018925:Chemokines; D016207:Cytokines; D018076:DNA, Complementary; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D008780:Methyltransferases; D050903:Nicotinamide N-Methyltransferase; C494407:Nnmt protein, mouse