Detection of an up-regulation of a group of chemokine genes in murine cardiac allograft in the absence of interferon-gamma by means of DNA microarray.
BACKGROUND
[corrected] Interferon (IFN)-gamma and the IFN-gamma-dependent pathway are prominent in vascularized allograft during acute rejection. However, IFN-gamma deficient (IFN-gamma-/-) mice can rapidly reject cardiac allografts. To bring the alternative pathway during allograft rejection into more precise focus, we investigated the gene expression profile in murine cardiac allografts in IFN-gamma-/- mice by means of DNA microarray.


METHODS
We screened for gene expression changes in murine cardiac allografts of BALB/c H-2d into both wild-type C57BL/6 H-2b (n=3) and IFN-gamma-/- C57BL/6 H-2b(IFN-gamma-/-, n=4) using Affymetrix oligonucleotide arrays to monitor more than 11,000 genes and expressed sequence tag (ESTs). The heart was heterotopically transplanted. Transplanted hearts were harvested on day 5. As a control, isografts (C57BL/6 to C57BL/6) were also harvested on day 5.


RESULTS
On day 5, 64 of the 84 genes induced in the allografts in wild-type mice were not up-regulated in IFN-gamma-/- mice. We identified a group of 54 genes that were up-regulated in allografts in IFN-gamma-/- mice. Several chemokine genes, including monocyte chemoattractant protein=1 and macrophage inflammatory protein, were induced in the allografts in both wild-type and IFN-gamma-/- mice. Interestingly, a group of genes, including C10-like chemokine and platelet factor 4, were specifically induced in the IFN-gamma-/- mice.


CONCLUSIONS
DNA microarray analysis reveals a unique pattern of mRNA expression in allografts in IFN-gamma-/- mice as well as a group of genes induced in cardiac allografts in both wild-type and IFN-gamma-/- mice, including monocyte chemoattractant protein-1 and monocyte chemoattractant protein-1.
Saiura
Akio
A
Department of Hepato-Biliary-Pancreatic and Transplantation Surgery, The University of Tokyo, Tokyo, Japan.
Kohro
Takahide
T
Yamamoto
Takashi
T
Izumi
Akashi
A
Wada
Yoichiro
Y
Aburatani
Hiroyuki
H
Sugawara
Yasuhiko
Y
Hamakubo
Takao
T
Taniguchi
Tadatsugu
T
Naito
Makoto
M
Kodama
Tatsuhiko
T
Makuuchi
Masatoshi
M
D000818:Animals; D015152:Blotting, Northern; D018932:Chemokine CCL2 / Q000235:genetics; D054407:Chemokine CCL4; D018925:Chemokines / Q000235:genetics*; D006085:Graft Survival; D016027:Heart Transplantation; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology*; D019402:Macrophage Inflammatory Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009206:Myocardium / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D019707:Receptors, Chemokine / Q000235:genetics; D012016:Reference Values; D014184:Transplantation, Homologous; D015854:Up-Regulation
D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018925:Chemokines; D019402:Macrophage Inflammatory Proteins; D019707:Receptors, Chemokine; D007371:Interferon-gamma