Open AccessAN OLIGONUCLEOTIDE BLOCKS INTERFERON-?? SIGNAL TRANSDUCTION1
Author(s) -
Peter P. Lee,
Murali Ramanathan,
C. Anthony Hunt,
Marvin R. Garovoy
Publication year - 1996
Publication title -
transplantation
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.45
H-Index - 204
eISSN - 1534-6080
pISSN - 0041-1337
DOI - 10.1097/00007890-199611150-00021
Subject(s) - oligonucleotide , intracellular , signal transduction , interferon , dna , nucleic acid , microbiology and biotechnology , biology , receptor , interferon gamma , mediator , aptamer , mechanism of action , cell , chemistry , immunology , cytokine , biochemistry , in vitro
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.