title: Up-regulation of reactive oxygen species (ROS) and resistance to Fas-mediated apoptosis in the C33A cervical cancer cell line transfected with IL-18 receptor.
abstract: Cervical cancer cells were transfected with a newly discovered interleukin (IL)-18 receptor to investigate the effect of endogenous IL-18 on the regulation of immune-related factors such as Fas (CD95/Apo-1)/Fas ligand and intercellular adhesion molecules. Transfection of the IL-18 receptor selectively induced a slight enhancement of the Fas via the up-regulation of intracellular reactive oxygen species and IL-18 in cervical carcinoma C33A cells, whereas there were no effects on the expression of p53, intercellular adhesion molecules-1 and Fas ligand. Neither IL-18 receptor transfection nor recombinant IL-18 enhanced interferon-gamma production in C33A cells. Thus, IL-18 receptor transfection induced IL-18 expression and enhanced intracellular reactive oxygen species and Fas expression in C33A cells in an interferon-gamma-independent pathway. However, treatment with agonistic anti-Fas antibody did not induce the apoptosis of C33A/IL-18 receptor transfectants, suggesting that either reactive oxygen species play a key role in resisting the Fas-induced apoptosis of C33A cells, or Fas was not functional. These results show that C33A/IL-18 receptor cells are resistant to the apoptosis and thus can survive against the immune surveillance and activated immune cells. Our results thus suggest that IL-18 and IL-18 receptor, together, may play a role in immunoregulation or in inflammation by augmenting the levels of IL-18 and reactive oxygen species in C33A cells.
authors.affiliation: Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea. dyyoon@kribb.re.kr
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Yoon-
authors.forename: Young-Sik
authors.initials: YS
authors.lastname: Cho
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Park
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Jong-Wan
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053727:Interleukin-18 Receptor alpha Subunit; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D011494:Protein Kinases / Q000276:immunology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000235:genetics / Q000502:physiology*; D053724:Receptors, Interleukin-18; D018124:Receptors, Tumor Necrosis Factor / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019014:fas Receptor
chemical_list: D000911:Antibodies, Monoclonal; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D007378:Interleukins; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D018799:Intercellular Adhesion Molecule-1; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases