Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays

Tamotsu Ichiba, Takanori Teshima, Rork Kuick, David E. Misek, Chen Liu, Yuichiro Takada, Yoshinobu Maeda, Pavan Reddy, Debra L. Williams, Samir M. Hanash, James L M Ferrara

Research output: Contribution to journalArticle

65 Citations (Scopus)

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 γ (IFN-γ)-inducible genes, major histocompatibility (MHC) class II molecules, and genes related to leukocyte trafficking had been up-regulated. Immunohistochemistry demonstrated that expression of IFN-γ 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-γ 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.

Original languageEnglish
Pages (from-to)763-771
Number of pages9
JournalBlood
Volume102
Issue number2
DOIs
Publication statusPublished - Jul 15 2003
Externally publishedYes

Fingerprint

Graft vs Host Disease
Microarrays
Oligonucleotide Array Sequence Analysis
Transcriptome
Gene expression
Grafts
Oligonucleotides
Bone
Genes
Liver
Bone Marrow Transplantation
Interferons
Homologous Transplantation
T-cells
Acute-Phase Proteins
Isogeneic Transplantation
Metabolism
MHC Class II Genes
Histocompatibility
Skin

ASJC Scopus subject areas

  • Hematology

Cite this

Ichiba, T., Teshima, T., Kuick, R., Misek, D. E., Liu, C., Takada, Y., ... Ferrara, J. L. M. (2003). Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays. Blood, 102(2), 763-771. https://doi.org/10.1182/blood-2002-09-2748

Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays. / Ichiba, Tamotsu; Teshima, Takanori; Kuick, Rork; Misek, David E.; Liu, Chen; Takada, Yuichiro; Maeda, Yoshinobu; Reddy, Pavan; Williams, Debra L.; Hanash, Samir M.; Ferrara, James L M.

In: Blood, Vol. 102, No. 2, 15.07.2003, p. 763-771.

Research output: Contribution to journalArticle

Ichiba, T, Teshima, T, Kuick, R, Misek, DE, Liu, C, Takada, Y, Maeda, Y, Reddy, P, Williams, DL, Hanash, SM & Ferrara, JLM 2003, 'Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays', Blood, vol. 102, no. 2, pp. 763-771. https://doi.org/10.1182/blood-2002-09-2748
Ichiba, Tamotsu ; Teshima, Takanori ; Kuick, Rork ; Misek, David E. ; Liu, Chen ; Takada, Yuichiro ; Maeda, Yoshinobu ; Reddy, Pavan ; Williams, Debra L. ; Hanash, Samir M. ; Ferrara, James L M. / Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays. In: Blood. 2003 ; Vol. 102, No. 2. pp. 763-771.
@article{62078cc12cd247d7bb3ba18dacad5136,
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 γ (IFN-γ)-inducible genes, major histocompatibility (MHC) class II molecules, and genes related to leukocyte trafficking had been up-regulated. Immunohistochemistry demonstrated that expression of IFN-γ 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-γ 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.",
author = "Tamotsu Ichiba and Takanori Teshima and Rork Kuick and Misek, {David E.} and Chen Liu and Yuichiro Takada and Yoshinobu Maeda and Pavan Reddy and Williams, {Debra L.} and Hanash, {Samir M.} and Ferrara, {James L M}",
year = "2003",
month = "7",
day = "15",
doi = "10.1182/blood-2002-09-2748",
language = "English",
volume = "102",
pages = "763--771",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "2",

}

TY - JOUR

T1 - Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays

AU - Ichiba, Tamotsu

AU - Teshima, Takanori

AU - Kuick, Rork

AU - Misek, David E.

AU - Liu, Chen

AU - Takada, Yuichiro

AU - Maeda, Yoshinobu

AU - Reddy, Pavan

AU - Williams, Debra L.

AU - Hanash, Samir M.

AU - Ferrara, James L M

PY - 2003/7/15

Y1 - 2003/7/15

N2 - 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 γ (IFN-γ)-inducible genes, major histocompatibility (MHC) class II molecules, and genes related to leukocyte trafficking had been up-regulated. Immunohistochemistry demonstrated that expression of IFN-γ 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-γ 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.

AB - 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 γ (IFN-γ)-inducible genes, major histocompatibility (MHC) class II molecules, and genes related to leukocyte trafficking had been up-regulated. Immunohistochemistry demonstrated that expression of IFN-γ 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-γ 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.

UR - http://www.scopus.com/inward/record.url?scp=0038494591&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038494591&partnerID=8YFLogxK

U2 - 10.1182/blood-2002-09-2748

DO - 10.1182/blood-2002-09-2748

M3 - Article

VL - 102

SP - 763

EP - 771

JO - Blood

JF - Blood

SN - 0006-4971

IS - 2

ER -