Soluble HLA-G induces NF-kappaB activation in natural killer cells.
Human leukocyte antigen (HLA)-G is an immunomodulatory molecule discovered for the first time in the maternal-fetal interface. In cancer context, where high number of natural killer (NK) cells is described, the presence of HLA-G in its soluble form is thought to be essential for NK cells signaling. To evaluate intracellular signaling in NK cells upon HLA-G soluble forms stimulation, we investigate the role of soluble HLA-G (HLA-G5- and HLA-G1 shedding form) stimulation on classical nuclear factor (NF)-kappaB pathway activation. We reported that these two forms of soluble HLA-G could activate NF-kappaB in NK cells. NF-kappaB activation in NK cells does implicate neither phosphatidylinositol 3-kinase (PI3K) nor MEK (MAP kinase kinase) as demonstrated after specific inhibition experiments. We demonstrated elsewhere that NF-kappaB activation in NK cells is not implicated in cytotoxicity inhibition by HLA-G. Our findings may suggest the important role played by NF-kappaB activation after soluble HLA-G stimulation in other NK cells function.
Zidi
I
I
Commissariat à l'Energie Atomique, Service de Recherches en Hémato-Immunologie, I2BM, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, 75010 Paris, France. ines.zidi@techemail.com
Guillard
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C
Carosella
E D
ED
Moreau
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P
D045744:Cell Line, Tumor; D006680:HLA Antigens / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D016328:NF-kappa B; D058539:Phosphatidylinositol 3-Kinase; D020929:Mitogen-Activated Protein Kinase Kinases
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