PROBLEM: The role of eukaryotic initiation factor 5A (eIF5A) in feto-maternal immunotolerance is poorly understood. METHODS OF STUDY: The effects of N1-guanyl-1,7-diaminoheptane (GC7), an inhibitor of eIF5A, on the proportion and function of natural killer (NK) cell subsets were investigated using flow cytometry, immunofluorescence, CCK8 assay, TUNEL assay, DNA fragmentation analysis, mitochondrial membrane potential assay, and Western blotting. RESULTS: Inhibition of eIF5A by GC7 increased embryo loss and reduced the percentage of NK cells in the uterus and spleen. GC7 treatment caused inhibition of NK cell proliferation in a time- and dose-dependent manner. GC7 also induced apoptosis of NK cells. GC7 treatment increased the protein levels of FasL, bax, p53, and cleaved caspase-3. Moreover, GC7 caused loss of mitochondrial membrane potential in NK cells. CONCLUSION: Inhibition of eIF5A results in aberrant NK cell function and increased embryo loss.
PROBLEM: The role of eukaryotic initiation factor 5A (eIF5A) in feto-maternal immunotolerance is poorly understood. METHODS OF STUDY: The effects of N1-guanyl-1,7-diaminoheptane (GC7), an inhibitor of eIF5A, on the proportion and function of natural killer (NK) cell subsets were investigated using flow cytometry, immunofluorescence, CCK8 assay, TUNEL assay, DNA fragmentation analysis, mitochondrial membrane potential assay, and Western blotting. RESULTS: Inhibition of eIF5A by GC7 increased embryo loss and reduced the percentage of NK cells in the uterus and spleen. GC7 treatment caused inhibition of NK cell proliferation in a time- and dose-dependent manner. GC7 also induced apoptosis of NK cells. GC7 treatment increased the protein levels of FasL, bax, p53, and cleaved caspase-3. Moreover, GC7 caused loss of mitochondrial membrane potential in NK cells. CONCLUSION: Inhibition of eIF5A results in aberrant NK cell function and increased embryo loss.
Authors: Bernhard Maier; Takeshi Ogihara; Anthony P Trace; Sarah A Tersey; Reiesha D Robbins; Swarup K Chakrabarti; Craig S Nunemaker; Natalie D Stull; Catherine A Taylor; John E Thompson; Richard S Dondero; Eli C Lewis; Charles A Dinarello; Jerry L Nadler; Raghavendra G Mirmira Journal: J Clin Invest Date: 2010-05-24 Impact factor: 14.808