title: An oligonucleotide blocks interferon-gamma signal transduction.
abstract: 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.
authors.affiliation: Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California, San Francisco 94143-0446, USA.
authors.forename: P P
authors.initials: PP
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Ramanathan
authors.forename: C A
authors.initials: CA
authors.lastname: Hunt
authors.forename: M R
authors.initials: MR
authors.lastname: Garovoy
mesh_terms: 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*
chemical_list: D009841:Oligonucleotides; D017471:Receptors, Interferon; D007371:Interferon-gamma