Detection of an up-regulation of a group of chemokine genes in murine cardiac allograft in the absence of interferon-?? by means of dna microarray1

Abstract

Interferon (IFN)-γ and the IFN-γ-dependent pathway are prominent in vascularized allograft during acute rejection. However, IFN-γ deficient (IFN-γ−/−) 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-γ−/− mice by means of DNA microarray. 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-γ−/− C57BL/6 H-2b(IFN-γ−/−, 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. On day 5, 64 of the 84 genes induced in the allografts in wild-type mice were not up-regulated in IFN-γ−/− mice. We identified a group of 54 genes that were up-regulated in allografts in IFN-γ−/− mice. Several chemokine genes, including monocyte chemoattractant protein=1 and macrophage inflammatory protein, were induced in the allografts in both wild-type and IFN-γ−/− mice. Interestingly, a group of genes, including C10-like chemokine and platelet factor 4, were specifically induced in the IFN-γ−/− mice. DNA microarray analysis reveals a unique pattern of mRNA expression in allografts in IFN-γ−/− mice as well as a group of genes induced in cardiac allografts in both wild-type and IFN-γ−/− mice, including monocyte chemoattractant protein-1 and monocyte chemoattractant protein-1.