title: Effects of transforming growth factor-beta 1 on nitric oxide synthesis by C2C12 skeletal myocytes.
abstract: The production of nitric oxide (NO) via the inducible form of NO synthase (iNOS) is regulated by a complex network of cytokines and endogenous hormones. Among these, transforming growth factor-beta (TGF-beta 1) is known to suppress iNOS expression and NO production by many cell types. To determine the effect of TGF-beta 1 on NO production by skeletal muscle cells, we stimulated C2C12 myocytes with interferon-gamma (IFN) and interleukin-1 (IL-1) in the presence or absence of TGF-beta 1. In contrast to findings in macrophages, TGF-beta 1 markedly enhanced NO production by skeletal muscle cells. Increases in NO production reflected significant increases in iNOS immunoreactive protein and iNOS mRNA. Elevated iNOS mRNA levels associated with TGF-beta 1 treatment were not due to an alteration in mRNA stability, but rather reflected a significantly increased transcriptional rate of the iNOS gene. These findings indicate that TGF-beta 1 enhances iNOS expression in skeletal muscle cells and suggest that the regulation of NO production by TGF-beta 1 may depend on the cell type studied.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063, USA.
authors.forename: G
authors.initials: G
authors.lastname: Williams
authors.forename: L
authors.initials: L
authors.lastname: Becker
authors.forename: D
authors.initials: D
authors.lastname: Bryant
authors.forename: S
authors.initials: S
authors.lastname: Willis
authors.forename: B P
authors.initials: BP
authors.lastname: Giroir
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D004357:Drug Synergism; D006207:Half-Life; D051379:Mice; D008809:Mice, Inbred C3H; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D009573:Nitrites; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase