title: Interferon-beta-1-b (IFN-B) decreases induced nitric oxide (NO) production by a human astrocytoma cell line.
abstract: Inducible nitric oxide synthase (iNOS) is expressed by astrocytes in demyelinating regions of multiple sclerosis (MS) brain plaques, suggesting that NO contributes to MS pathology. Since the immunosuppressive cytokine IFN-B ameliorates MS disease activity, it is of interest to assess the modulatory role of IFN-B on NO production. We studied the effects of IFN-B, as well as dexamethasone, IL-10, and transforming growth factor-beta (TGF-B), on cytokine-induced NO production by the human astrocytoma cell line, A172. L-NMMA and aminoguanidine, competitive inhibitors of iNOS suppressed NO production as measured by the NO byproduct, nitrite, as did IFN-B. Dexamethasone enhanced NO production, and IFN-B decreased the amount of the enhancement. Neither IL-10 nor TGF-B inhibited nitrite production. The therapeutic effect of IFN-B in MS may be partly due to suppression of pathogenic NO production.
authors.affiliation: Student School of Dentistry, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: P
authors.initials: P
authors.lastname: Guthikonda
authors.forename: J
authors.initials: J
authors.lastname: Baker
authors.forename: D H
authors.initials: DH
authors.lastname: Mattson
mesh_terms: D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018836:Inflammation Mediators / Q000494:pharmacology; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D014407:Tumor Cells, Cultured
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D000068576:Interferon beta-1b; D009569:Nitric Oxide; D016899:Interferon-beta; D003907:Dexamethasone; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D000068556:Interferon beta-1a