Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 6, Issue 6, Pages 1342-1354Publisher
WILEY
DOI: 10.1111/j.1600-6143.2006.01337.x
Keywords
Gene expression; interferon gamma; microarray; mouse kidney; post-operative injury; rejection
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We used Affymetrix Microarrays to define interferon-gamma (IFN-gamma)-dependent, rejection-induced transcripts (GRITs) in mouse kidney allografts. The algorithm included inducibility by recombinant IFN-gamma in kidneys of three normal mouse strains, increase in kidney allografts in three strain combinations and less induction in IFN-gamma-deficient allografts. We identified 40 transcripts, which were highly IFN-gamma inducible (e.g. Cxcl9, ubiquitin D, MHC), and 168 less sensitive to IFN-gamma in normal kidney. In allografts, expression of GRITs was intense and consistent at all time points (day 3 through 42). These transcripts were partially dependent on donor IFN-gamma receptors (IFN-gamma rs): receptor-deficient allografts manifested up to 76% less expression, but some transcripts were highly dependent (ubiquitin D) and others relatively independent (Cxcl9). Kidneys of hosts rejecting allografts showed expression similar to that observed with IFN-gamma injections. Many GRITs showed transient IFN-gamma-dependent increase in isografts, peaking at day 4-5. GRITs were increased in heart allografts, indicating them as generalized feature of alloresponse. Thus, expression of rejection-induced transcripts is robust and consistent in allografts, reflecting the IFN-gamma produced by the alloresponse locally and systemically, acting via host and donor IFN-gamma r, as well as local IFN-gamma production induced by post-operative stress.
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