title: Interleukin-1 (IL-1)-induced IL-6- and IL-6-receptor-mediated release of human chorionic gonadotropin by choriocarcinoma cell lines (Jar and HCCM-5) activates adenosine 3',5'-monophosphate-independent signal transduction pathway.
abstract: The status of preservation of the ability to secrete cytokines, such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF alpha), and IL-6, and the cytokine-mediated regulatory cascade was investigated in four choriocarcinoma cell lines. Each cell line constitutively produced IL-6, but not IL-1 alpha, IL-1 beta, or TNF alpha. Jar and HCCM-5 cells responded to IL-6, releasing hCG by direct activation of IL-6 receptors (IL-6-R) with IL-6. Both cell lines also responded to IL-1, but failed to responded to TNF alpha. When stimulated with recombinant IL-1 alpha, both cell lines released IL-6 and activated the IL-6-R system to release hCG, whereas stimulation with TNF alpha failed to release hCG. The experiments showed that both the Jar and HCCM-5 cell lines possessed a partially intact cytokine-mediated cascade, suggesting that IL-1-induced IL-6 release and IL-6-R activation operate in an autocrine manner. In contrast, NUC-1 and SCH cells failed to respond to IL-6, IL-1, or TNF alpha. Although 8-bromo-cAMP, which is a cAMP analog, stimulates hCG release by Jar cells, it failed to stimulate IL-6 release. Moreover, cAMP-mediated hCG release was not blocked by PM1, an anti-IL-6-R antibody. This suggests that elevation of the cytoplasmic cAMP level might activate a pathway different from the IL-6- and IL-6-R-dependent pathway. Moreover, IL-1- and IL-6-mediated hCG release was not blocked by H8, a cAMP-dependent kinase inhibitor, which further suggests that the IL-1- and IL-6-mediated pathway functions independently of the cAMP-dependent pathway in releasing hCG in Jar cells.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: N
authors.initials: N
authors.lastname: Matsuzaki
authors.forename: T
authors.initials: T
authors.lastname: Jo
authors.forename: F
authors.initials: F
authors.lastname: Saji
authors.forename: T
authors.initials: T
authors.lastname: Taga
authors.forename: T
authors.initials: T
authors.lastname: Hirano
authors.forename: T
authors.initials: T
authors.lastname: Kishimoto
authors.forename: O
authors.initials: O
authors.lastname: Tanizawa
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D002460:Cell Line; D002822:Choriocarcinoma; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D011247:Pregnancy; D047428:Protein Kinase Inhibitors; D011971:Receptors, Immunologic / Q000187:drug effects / Q000502:physiology*; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014594:Uterine Neoplasms
chemical_list: D006063:Chorionic Gonadotropin; D007375:Interleukin-1; D015850:Interleukin-6; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015124:8-Bromo Cyclic Adenosine Monophosphate; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D000242:Cyclic AMP