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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal / pharmacology
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Apoptosis / drug effects
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Apoptosis / physiology*
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Blotting, Northern
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Blotting, Western
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Cell Line, Tumor
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Enzyme-Linked Immunosorbent Assay
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Fas Ligand Protein
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Female
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Flow Cytometry
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Gene Expression
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Genetic Vectors / genetics
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Humans
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Intercellular Adhesion Molecule-1 / metabolism
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Interleukin-1 Receptor-Associated Kinases
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Interleukin-18 / genetics
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Interleukin-18 / immunology
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Interleukin-18 / metabolism*
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Interleukin-18 Receptor alpha Subunit
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Interleukins / immunology
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Interleukins / metabolism
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Membrane Glycoproteins / metabolism
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Protein Kinases / immunology
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Protein Kinases / metabolism
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Reactive Oxygen Species / metabolism*
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Receptors, Interleukin / genetics
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Receptors, Interleukin / physiology*
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Receptors, Interleukin-18
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Receptors, Tumor Necrosis Factor / agonists
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Receptors, Tumor Necrosis Factor / metabolism
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Receptors, Tumor Necrosis Factor / physiology*
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Reverse Transcriptase Polymerase Chain Reaction
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Transfection
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Suppressor Protein p53 / metabolism
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Up-Regulation
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Uterine Cervical Neoplasms / genetics
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Uterine Cervical Neoplasms / metabolism
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Uterine Cervical Neoplasms / pathology
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fas Receptor
Substances
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Antibodies, Monoclonal
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FAS protein, human
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FASLG protein, human
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Fas Ligand Protein
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IL18R1 protein, human
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Interleukin-18
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Interleukin-18 Receptor alpha Subunit
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Interleukins
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Membrane Glycoproteins
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Reactive Oxygen Species
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Receptors, Interleukin
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Receptors, Interleukin-18
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Receptors, Tumor Necrosis Factor
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Tumor Necrosis Factor-alpha
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Tumor Suppressor Protein p53
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fas Receptor
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Intercellular Adhesion Molecule-1
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Protein Kinases
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Interleukin-1 Receptor-Associated Kinases