Growth and apoptosis of human natural killer cell neoplasms: role of interleukin-2/15 signaling.
Interleukin (IL)-15 plays an important role in the survival of human natural killer (NK) cells. We investigated IL-2/15 signaling in NK cell neoplasms from five patients and in five cell lines (NK-92, KHYG-1, SNK-6, HANK1 and MOTN-1) compared to mature peripheral NK cells from 10 healthy subjects. Apoptosis of NK cell lines was prevented by addition of IL-15 in vitro. Blocking IL-2/15Rbeta on IL-2-stimulated NK-92 cells resulted in reduced expression of Bcl-X(L) and phosphorylated Stat5, which paralleled early apoptosis without altering Bcl-2 expression. These data add IL-2/15Rbeta to the list of factors important for the survival of NK cell neoplasms.
Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Fukuoka, Japan. yamasaki@1nai.med.kyushu-u.ac.jp
Satoshi
S
Yamasaki
Motoi
M
Maeda
Koichi
K
Ohshima
Masahiro
M
Kikuchi
Teruhisa
T
Otsuka
Mine
M
Harada
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D019409:Interleukin-15 / Q000096:biosynthesis / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D007938:Leukemia / Q000276:immunology* / Q000473:pathology; D008223:Lymphoma / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D053647:Receptors, Interleukin-15 / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; C494826:BAX protein, human; D019409:Interleukin-15; D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D051028:bcl-2-Associated X Protein