title: Regulation of interleukin-6 secretion in murine pituicytes.
abstract: Pituicytes, the astrocytic glial cells of the neural lobe, are known to secrete interleukin-6 and nitric oxide upon stimulation with various inflammatory mediators, i.e. interleukin-1beta. Nitric oxide is described to modulate the secretion of interleukin-6 in various cell types. The aim of the present study was to investigate the effect of nitric oxide on interleukin-1beta induced interleukin-6 secretion. Furthermore the effect of interferon-gamma on interleukin-6 and nitric oxide release was investigated. Cultures of pituicytes were prepared of neural lobes from male mice. The effect of interleukin-1beta and interferon-gamma on interleukin-6 and nitric oxide secretion was investigated in pituicytes cultured for 14 days. The secretion of interleukin-6 and nitric oxide was determined after 24 h of stimulation. Pituicytes secrete interleukin-6 upon stimulation with interleukin-1beta dose dependently but did not induce any detectable nitric oxide release. Co-stimulation with interferon-gamma and interleukin-1beta induced a significant nitric oxide release. In addition interferon-gamma inhibits interleukin-1beta induced interleukin-6 secretion dose dependently. The observed effect of interferon-gamma on interleukin-6 secretion was not affected by the specific inducible nitric oxide synthase inhibitor 1400W (N-(3-[aminomethyl]benzyl)acetamidine). Furthermore interferon-gamma dose dependently inhibits unstimulated interleukin-6 secretion. Use of the nitric oxide releaser DETA/NO (2,2'-(hydroxynitrosohydrazono)bis-ethanimine) demonstrated that nitric oxide does not inhibit interleukin-1beta induced interleukin-6 secretion. These results demonstrated that nitric oxide has no influence on interleukin-1beta induced interleukin-6 secretion in cultured pituicytes. However the results are showing that interferon-gamma has an inhibitory effect on interleukin-6 secretion.
authors.affiliation: The Danish University of Pharmaceutical Sciences, Department of Pharmacology, 2 Universitetsparken, DK-2100 Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Thorn
authors.forename: Mikkel
authors.initials: M
authors.lastname: Tuxen
authors.forename: Lise
authors.initials: L
authors.lastname: Moesby
authors.forename: Erik W
authors.initials: EW
authors.lastname: Hansen
authors.forename: Jens D
authors.initials: JD
authors.lastname: Christensen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007097:Imines / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009603:Nitroso Compounds / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D007097:Imines; D007375:Interleukin-1; D015850:Interleukin-6; C496401:N-((3-(aminomethyl)phenyl)methyl)ethanimidamide; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase