Journal
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
Volume 71, Issue 3, Pages 229-240Publisher
WILEY
DOI: 10.1111/aji.12194
Keywords
Abortion; apoptosis; eIF5A; GC7; natural killer cell
Categories
Funding
- National Basic Research Program of China [2013CB967401, 2013CB967404]
- National Funds for Distinguished Young Scientists, China [81125004]
- National Natural Science Foundation of China [31171439]
- Funds for Outstanding Academic Leaders in Shanghai, China [12XD1406600]
- Frontier Technology Joint Research Program for Shanghai Municipal Hospitals, Shanghai, China [SHDC12010122]
- Superfund Program Research National Institute of Environmental Health Sciences, USA (SPR NIEH) [P42ES013660]
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Problem The role of eukaryotic initiation factor 5A (eIF5A) in feto-maternal immunotolerance is poorly understood. Methods of studyThe 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. ResultsInhibition 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. ConclusionInhibition of eIF5A results in aberrant NK cell function and increased embryo loss.
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