Interleukin 18 enhances Fas ligand expression and induces apoptosis in Fas-expressing human myelomonocytic KG-1 cells.
Interleukin-18 (IL-18) induces apoptosis in human myelomonocytic KG-1 cells as determined by agarose gel electrophoresis, and flow cytometry after propidium iodide (PI) staining. Apoptosis was detected 20 hours from the start of culture at concentrations of 100 ng/ml of the cytokine. Although IL-18 induces the production of large amounts of interferon gamma (IFN-gamma) by KG-1 cells, conditioned media could not induce apoptosis of fresh cells. The protein expressions of p53 and Fas ligand by KG-1 cells, which constitutively express the Fas antigen (CD95), were found to increase after exposure to IL-18 for 20 hours. Both Fas ligand and its receptor were found to be functional by in vitro assays on Fas-expressing target cells and an agonist anti-Fas antibody, respectively. In conclusion, IL-18 enhances the expression of Fas ligand by Fas-expressing KG-1 cells and induces apoptosis in the cells through a mechanism probably involving the Fas pathway.
Ohtsuki
T
T
Fujisaki Institute, Hayashibara Biochemical Laboratories Inc., Okayama, Japan.
Micallef
M J
MJ
Kohno
K
K
Tanimoto
T
T
Ikeda
M
M
Kurimoto
M
M
D017209:Apoptosis; D016207:Cytokines / Q000502:physiology*; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000378:metabolism; D053222:Fas Ligand Protein; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D020382:Interleukin-18; D015479:Leukemia, Myelomonocytic, Acute / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D014407:Tumor Cells, Cultured
D016207:Cytokines; D004273:DNA, Neoplasm; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D020382:Interleukin-18; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D007371:Interferon-gamma