PMID- 1317386 OWN - NLM STAT- MEDLINE DCOM- 19920629 LR - 20181130 IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 74 IP - 6 DP - 1992 Jun TI - 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. PG - 1389-95 AB - 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. FAU - Taniguchi, T AU - Taniguchi T AD - Department of Obstetrics and Gynecology, Osaka University Medical School, Japan. FAU - Matsuzaki, N AU - Matsuzaki N FAU - Jo, T AU - Jo T FAU - Saji, F AU - Saji F FAU - Taga, T AU - Taga T FAU - Hirano, T AU - Hirano T FAU - Kishimoto, T AU - Kishimoto T FAU - Tanizawa, O AU - Tanizawa O LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Chorionic Gonadotropin) RN - 0 (Interleukin-1) RN - 0 (Interleukin-6) RN - 0 (Isoquinolines) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Receptors, Immunologic) RN - 0 (Receptors, Interleukin-6) RN - 0 (Recombinant Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 23583-48-4 (8-Bromo Cyclic Adenosine Monophosphate) RN - 84478-11-5 (N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide) RN - E0399OZS9N (Cyclic AMP) SB - IM MH - 8-Bromo Cyclic Adenosine Monophosphate/*pharmacology MH - Cell Line MH - Choriocarcinoma MH - Chorionic Gonadotropin/*metabolism MH - Cyclic AMP/metabolism/*pharmacology MH - Female MH - Humans MH - Interleukin-1/metabolism/*pharmacology MH - Interleukin-6/biosynthesis/*pharmacology/physiology MH - Isoquinolines/pharmacology MH - Kinetics MH - Pregnancy MH - Protein Kinase Inhibitors MH - Receptors, Immunologic/drug effects/*physiology MH - Receptors, Interleukin-6 MH - Recombinant Proteins/pharmacology MH - Signal Transduction/*physiology MH - Tumor Necrosis Factor-alpha/pharmacology MH - Uterine Neoplasms EDAT- 1992/06/01 00:00 MHDA- 1992/06/01 00:01 CRDT- 1992/06/01 00:00 PHST- 1992/06/01 00:00 [pubmed] PHST- 1992/06/01 00:01 [medline] PHST- 1992/06/01 00:00 [entrez] AID - 10.1210/jcem.74.6.1317386 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 1992 Jun;74(6):1389-95. doi: 10.1210/jcem.74.6.1317386.