Activated endothelial cells induce apoptosis in leukemic cells by endothelial interleukin-8.
Tumor cells are eradicated by several systems, including Fas ligand-Fas and tumor necrosis factor (TNF)-tumor necrosis factor receptor (TNFR). In the previous study, we purified an apoptosis-inducing factor (AIF) to homogeneity from a medium conditioned by PDBu-treated HL-60 cells. N-terminal sequence analysis showed that AIF is identical to endothelial interleukin-8 (IL-8). A novel apoptosis system, in which endothelial cells participate via endothelial IL-8 release, is identified here. Human umbilical vein cells (VE cells) produce and secrete IL-8 by stimulation of IL-1alpha and TNF-alpha. Endothelial IL-8, which is secreted from VE cells by stimulation of IL-1alpha and TNF-alpha , induces apoptosis in myelogenous leukemia cell line K562 cells. Monocyte-derived IL-8 could not induce apoptosis in K562 cells. Moreover, interaction between VE cells and K562 cells induces the release of endothelial IL-8 from VE cells, and the attached K562 cells undergo apoptosis. Moreover, interactions between VE cell and other cell lines, such as HL-60, U937, Jurkat, and Daudi, induce the secretion of endothelial IL-8 and the induction of apoptosis in cell lines. Endothelial IL-8 significantly inhibits tumor growth of intraperitoneal and subcutaneous tumor mass of K562 cells and induces apoptosis in their cells in vivo. Endothelial IL-8 plays an important role in apoptosis involving endothelial cells, which may provide us with a new therapy for hematological malignancies.
Division of Hematology, Department of Internal Medicine, Jichi Medical School, Kawachi-gun, Tochigi, Japan.
Y
Y
Terui
M
M
Ikeda
H
H
Tomizuka
T
T
Kasahara
T
T
Ohtsuki
M
M
Uwai
M
M
Mori
T
T
Itoh
M
M
Tanaka
M
M
Yamada
S
S
Shimamura
Y
Y
Ishizaka
K
K
Ikeda
K
K
Ozawa
Y
Y
Miura
K
K
Hatake
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D018922:HL-60 Cells / Q000473:pathology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D019169:Jurkat Cells / Q000473:pathology; D020014:K562 Cells / Q000473:pathology; D007938:Leukemia / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins
D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor