title: Proinflammatory cytokines interact synergistically with epidermal growth factor to stimulate PGE2 production in amnion-derived cells.
abstract: Recent evidence has implicated cytokines and growth factors in the initiation of parturition in women. In the present study, the amnion-derived cell line WISH was used to determine whether proinflammatory cytokines (interleukins 1 beta, 6, and 8, tumor necrosis factor-alpha, and granulocyte/macrophage colony stimulating factor) could amplify epidermal growth factor-induced prostaglandin E2 production. WISH cells were preincubated with cytokines (0.0001-10 ng/ml) for 60 min and then challenged with EGF (10 ng/ml) for 4 hrs after which PGE2 production was measured by radioimmunoassay. EGF, IL-1 beta and TNF-alpha alone caused a dose-dependent increase in PGE2 production, while IL-6, IL-8 and GM-CSF were ineffective over the dose range tested. When cells were preincubated with IL-1 beta or TNF-alpha, there was a dose-dependent potentiation of EGF-induced PGE2 production that was greater than the sum of EGF alone and IL-1 beta or TNF-alpha alone. In each case, the minimum dose of IL-1 beta or TNF-alpha which amplified EGF-induced PGE2 production was 0.1 ng/ml (p less than 0.05, Student's t-test). These data show that low concentrations of IL-1 beta or TNF-alpha may serve to amplify EGF-mediated PGE2 biosynthesis in amnion-derived cells and suggest that cytokines may modulate EGF function in responsive cells.
authors.affiliation: Department of Obstetrics and Gynecology (Division of Maternal-Fetal Medicine), Ohio State University College of Medicine, Columbus 43210.
authors.forename: D A
authors.initials: DA
authors.lastname: Kniss
authors.forename: P D
authors.initials: PD
authors.lastname: Zimmerman
authors.forename: R H
authors.initials: RH
authors.lastname: Fertel
authors.forename: J D
authors.initials: JD
authors.lastname: Iams
mesh_terms: D000650:Amnion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D015232:Dinoprostone / Q000032:analysis / Q000096:biosynthesis*; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D011247:Pregnancy; D011863:Radioimmunoassay
chemical_list: D016207:Cytokines; D004815:Epidermal Growth Factor; D015232:Dinoprostone