Interferon-beta-1-b (IFN-B) decreases induced nitric oxide (NO) production by a human astrocytoma cell line.
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.
Guthikonda
P
P
Student School of Dentistry, University of Pennsylvania, Philadelphia 19104, USA.
Baker
J
J
Mattson
D H
DH
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
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