Inhibition by interleukin-18 of the growth of Dunn osteosarcoma cells.
To examine the usefulness of interleukin-18 (IL-18) in the treatment of osteosarcomas, the effect of IL-18 on the growth of Dunn osteosarcoma cells was investigated. Daily intraperitoneal (i.p.) injection of mouse recombinant IL-18 (2 microg/mouse) suppressed the growth of Dunn osteosarcoma cells transplanted subcutaneously (s.c.) into syngeneic C3H mice. This IL-18-induced suppression was not affected by simultaneous treatment with anti-asialo GM1 serum, which inactivates natural killer (NK) cells. However, IL-18 failed to suppress the growth of Dunn osteosarcoma cells transplanted into BALB/c-nude mice devoid of T lymphocytes or C3H-gld/gld mice deficient in functional Fas ligand (FasL). IL-18 also failed to suppress the growth of Dunn osteosarcoma cells in vitro, although expression of IL-18 receptor mRNA and MyD88 mRNA as well as Fas mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). On the other hand, antimouse Fas antibody showed cytotoxicity against Dunn osteosarcoma cells in a dose-dependent manner in vitro. In addition, treatment of C3H mice with IL-18 enhanced the cytotoxic activity of CD8(+) T lymphocytes against Dunn osteosarcoma cells. These results indicate that IL-18 inhibits the growth of Dunn osteosarcoma cells in vivo by enhancing the cytotoxic activity of CD8(+) T lymphocytes through the FasL-Fas system.
Okamoto
Takuya
T
Departments of Pathology and Orthopedic Surgery, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Hyogo 663-8501, Japan.
Yamada
Naoko
N
Tsujimura
Tohru
T
Sugihara
Ayako
A
Nishizawa
Yasuko
Y
Ueda
Haruyasu
H
Kashiwamura
Shin-Ichiro
S
Tsutsui
Hiroko
H
Futani
Hiroyuki
H
Maruo
Souji
S
Okamura
Haruki
H
Terada
Nobuyuki
N
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000906:Antibodies / Q000633:toxicity; D000943:Antigens, Differentiation / Q000235:genetics; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D002455:Cell Division; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D053222:Fas Ligand Protein; D005677:G(M1) Ganglioside / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D020382:Interleukin-18 / Q000493:pharmacokinetics / Q000627:therapeutic use*; D053727:Interleukin-18 Receptor alpha Subunit; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D053594:Myeloid Differentiation Factor 88; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D053724:Receptors, Interleukin-18; D013601:T-Lymphocytes / Q000187:drug effects; D019014:fas Receptor / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D000943:Antigens, Differentiation; D000970:Antineoplastic Agents; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C508573:Il18r1 protein, mouse; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D019014:fas Receptor; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside