title: Production of interleukin (IL)-6 and IL-8 by a choriocarcinoma cell line, BeWo.
abstract: To clarify the biological and pathological features of choriocarcinoma, we evaluated the in vitro production of cytokines by a choriocarcinoma cell line, BeWo. We measured the concentration of interleukin (IL)-6 and IL-8 in the culture media of BeWo cells after stimulation with various modulatory agents of cytokine expression by enzyme-linked immunosorbent assays. Northern blot analysis was used to examine the expression of IL-6 and IL-8 mRNA in these cells. A weak expression of IL-6 and IL-8 was detected in unstimulated BeWo cells by both methods. IL-6 transcription and secretion were dose-dependently enhanced by stimulation with IL-1beta, tumour necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1 and 12-O-tetradecanoyl phorbol-13-acetate (TPA). Forskolin, lipopolysaccharide and interferon-gamma had no effect on these cytokines production. The TNF-alpha-induced secretion of IL-6 was inhibited by dexamethasone. The TPA-induced production of IL-6 was inhibited by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine and sphyngosine, suggesting the involvement of a protein kinase C-dependent pathway. Levels of IL-8 mRNA and protein were also dose-dependently increased by stimulation with IL-1beta, TNF-alpha and TPA. In contrast to IL-6, the expression of IL-8 was not affected by TGF-beta1. It is suggested that, in addition to the production of steroidal and non-steroidal hormones, these cytokines may serve as part of a cytokine network that modulates the proliferation and angiogenesis of choriocarcinomas.
authors.affiliation: Department of Obstetrics and Gynecology, Oita Medical University, Hasama-machi, Oita, 879-5593, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fujisawa
authors.forename: K
authors.initials: K
authors.lastname: Nasu
authors.forename: K
authors.initials: K
authors.lastname: Arima
authors.forename: T
authors.initials: T
authors.lastname: Sugano
authors.forename: H
authors.initials: H
authors.lastname: Narahara
authors.forename: I
authors.initials: I
authors.lastname: Miyakawa
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000328:Adult; D015152:Blotting, Northern; D002822:Choriocarcinoma / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D013110:Sphingosine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014594:Uterine Neoplasms / Q000378:metabolism*; D000093242:Interleukin-6 Inhibitors
chemical_list: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D003907:Dexamethasone; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C080501:1-(5-isoquinolinylsulfonyl)-3-methylpiperazine