An oligonucleotide blocks interferon-gamma signal transduction.
Interferon (IFN)-gamma is an important mediator of transplant graft rejection. It induces endothelial cell expression of HLA-DR and intercellular adhesion molecule-1, which render transplant grafts more susceptible to rejection by the host. Oligonucleotide 5'-GGG GTT GGT TGT GTT GGG TGT TGT GT-RNH2 (oligo I) blocks multiple IFN-gamma effects in human K562 cell cultures. A systematic approach revealed that oligo I has a novel, and potentially important, mode of action--it blocks the binding of IFN-gamma to its receptor, thus preventing activation of the IFN-gamma signal transduction pathway. The results are consistent with an aptamer mechanism of action, because oligo I exerts its inhibitory effects by interacting with protein, not intracellular nucleic acid targets, such as mRNA or genomic DNA.
Lee
P P
PP
Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California, San Francisco 94143-0446, USA.
Ramanathan
M
M
Hunt
C A
CA
Garovoy
M R
MR
D002460:Cell Line; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D009841:Oligonucleotides / Q000494:pharmacology*; D017471:Receptors, Interferon / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D009841:Oligonucleotides; D017471:Receptors, Interferon; D007371:Interferon-gamma