title: Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays.
abstract: The liver, skin, and gastrointestinal tract are major target organs of acute graft-versus-host disease (GVHD), the major complication of allogeneic bone marrow transplantation (BMT). In order to gain a better understanding of acute GVHD in the liver, we compared the gene expression profiles of livers after experimental allogeneic and syngeneic BMT using oligonucleotide microarray. At 35 days after allogeneic BMT when hepatic GVHD was histologically evident, genes related to cellular effectors and acute-phase proteins were up-regulated, whereas genes largely related to metabolism and endocrine function were down-regulated. At day 7 after BMT before the development of histologic changes in the liver, interferon gamma (IFN-gamma)-inducible genes, major histocompatibility (MHC) class II molecules, and genes related to leukocyte trafficking had been up-regulated. Immunohistochemistry demonstrated that expression of IFN-gamma protein itself was increased in the spleen but not in hepatic tissue. These results suggest that the increased expression of genes associated with the attraction and activation of donor T cells induced by IFN-gamma early after BMT is important in the initiation of hepatic GVHD in this model and provide new potential molecular targets for early detection and intervention of acute GVHD.
authors.affiliation: Department of Internal Medicine, University of Michigan Cancer Center, Ann Arbor, USA.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Ichiba
authors.forename: Takanori
authors.initials: T
authors.lastname: Teshima
authors.forename: Rork
authors.initials: R
authors.lastname: Kuick
authors.forename: David E
authors.initials: DE
authors.lastname: Misek
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Takada
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Maeda
authors.forename: Pavan
authors.initials: P
authors.lastname: Reddy
authors.forename: Debra L
authors.initials: DL
authors.lastname: Williams
authors.forename: Samir M
authors.initials: SM
authors.lastname: Hanash
authors.forename: James L M
authors.initials: JL
authors.lastname: Ferrara
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002634:Chemotaxis, Leukocyte / Q000235:genetics; D020224:Expressed Sequence Tags; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006086:Graft vs Host Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D011828:Radiation Chimera; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous / Q000009:adverse effects; D014185:Transplantation, Isogeneic
chemical_list: D000209:Acute-Phase Proteins; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma