Cytokine regulation of HLA-G expression in human trophoblast cell lines.
HLA class I genes are differentially expressed among subpopulations of cells in first trimester human placentas. In this study, HLA class I protein was detected in extravillous cytotrophoblast cells by immunohistochemistry using the monoclonal antibody W6/32. In the same trophoblast subpopulation, class Ib proteins were identified with two monoclonal antibodies, 87G (anti-HLA-G) and 131 (anti-HLA-A/G) and class Ia protein was detected with the monoclonal antibody, 4E (anti-HLA-B/C). All of the antibodies also identified antigens on the human trophoblast-derived choriocarcinoma cell line, JEG-3. Therefore, the JEG-3 cells were used as a model system to study cytokine regulation of HLA-G in trophoblast cells. Northern blot hybridization studies showed that interferons (IFN-alpha, IFN-beta, IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) modestly enhanced steady state levels of HLA-G mRNA. Yet analysis of HLA-G protein by immunocytochemistry and flow cytometry failed to identify any changes in intracellular or membrane expression of HLA-G protein following cytokine treatment. Resistance to upregulation of HLA class I antigens was not a general feature of JEG-3 cells; IFNs enhanced expression of HLA-B/C as well as HLA class I light chain, beta 2-microglobulin. HLA null Jar choriocarcinoma cells did not contain HLA-G mRNA or antigen and exposure to cytokines had no effect on HLA-G. The results of this study are consistent with the postulate that trophoblast cell expression of HLA-G is stringently regulated and is controlled in part by post-transcriptional mechanisms.
Yang
Y
Y
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City 66160-7400, USA.
Geraghty
D E
DE
Hunt
J S
JS
D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006680:HLA Antigens / Q000032:analysis* / Q000235:genetics; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D014327:Trophoblasts / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma