Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays.
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.
Ichiba
Tamotsu
T
Department of Internal Medicine, University of Michigan Cancer Center, Ann Arbor, USA.
Teshima
Takanori
T
Kuick
Rork
R
Misek
David E
DE
Liu
Chen
C
Takada
Yuichiro
Y
Maeda
Yoshinobu
Y
Reddy
Pavan
P
Williams
Debra L
DL
Hanash
Samir M
SM
Ferrara
James L M
JL
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
D000209:Acute-Phase Proteins; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma