Effects of transforming growth factor-beta 1 on nitric oxide synthesis by C2C12 skeletal myocytes.
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.
Williams
G
G
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063, USA.
Becker
L
L
Bryant
D
D
Willis
S
S
Giroir
B P
BP
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*
D016207:Cytokines; D009573:Nitrites; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase