A comparison of gene expression in murine cardiac allografts and isograftsby means dna microarray analysis

Citation
A. Saiura et al., A comparison of gene expression in murine cardiac allografts and isograftsby means dna microarray analysis, TRANSPLANT, 72(2), 2001, pp. 320-329
Citations number
22
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medical Research Diagnosis & Treatment
Journal title
TRANSPLANTATION
ISSN journal
0041-1337 → ACNP
Volume
72
Issue
2
Year of publication
2001
Pages
320 - 329
Database
ISI
SICI code
0041-1337(20010727)72:2<320:ACOGEI>2.0.ZU;2-Q
Abstract
Background. Acute rejection of allografts remains a significant problem in clinical transplantation, and the fundamental mechanism underlying this rej ection are as yet only poorly elucidated. Recently, DNA microarrays have co me into use for the study of gene expression profiles, and we have taken ad vantage of this new technology to investigate acute rejection. We compared mRNA profiles in murine cardiac allografts with isografts using DNA microar rays with probe sets corresponding to more than 11,000 mice genes. Methods. We screened for gene expression changes in murine cardiac allograf ts between fully incompatible mice strains (BALB/c H2(d) to C3H/He H2(k)) u sing a DNA microarray. The heart was heterotopically transplanted. Allograf ts (BALB/c to C3H/He) were removed on days 1, 3, and 5. As a control, isogr afts (C3H/He to C3H/He) harvested on days 1, 3, and 5 and native hearts of both strain mice (C3H/He and BALB/c) were obtained. Results. On day 5, interferon-gamma (IFN-gamma) and many IFN-gamma -inducib le genes were profoundly induced in the allograft relative to isograft, Mon okine induced by IFN-gamma was most profoundly induced followed by inducibl y expressed GTPase and Lmp-2. IFN-gamma was also profoundly induced. The in duction was detectable from day 3. In contrast, genes regulated by other cy tokines exhibited only modest changes. Conclusion. IFN-gamma -inducible genes are specifically up-regulated in mur ine cardiac allografts, suggesting that signaling mediated by IFN-gamma may play an important role in the late phase of acute rejection in vivo.