title: Inhibition by interleukin-18 of the growth of Dunn osteosarcoma cells.
abstract: 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.
authors.affiliation: Departments of Pathology and Orthopedic Surgery, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Okamoto
authors.forename: Naoko
authors.initials: N
authors.lastname: Yamada
authors.forename: Tohru
authors.initials: T
authors.lastname: Tsujimura
authors.forename: Ayako
authors.initials: A
authors.lastname: Sugihara
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Ueda
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Kashiwamura
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Futani
authors.forename: Souji
authors.initials: S
authors.lastname: Maruo
authors.forename: Haruki
authors.initials: H
authors.lastname: Okamura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Terada
mesh_terms: 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
chemical_list: 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