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 synth ase (iNOS) is regulated by a complex network of cytokines and endogeno us hormones. Among these, transforming growth factor-beta (TGF-beta 1) is known to suppress iNOS expression and NO production by many cell t ypes. To determine the effect of TGF-beta 1 on NO production by skelet al muscle cells, we stimulated C2C12 myocytes with interferon-gamma (I FN) 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 ref lected significant increases in iNOS immunoreactive protein and iNOS m RNA. Elevated iNOS mRNA levels associated with TGF-beta 1 treatment we re not due to an alteration in mRNA stability, but rather reflected a significantly increased transcriptional rate of the iNOS gene. These f indings indicate that TGF-beta 1 enhances iNOS expression in skeletal muscle cells and suggest that the regulation of NO production by TFG-b eta 1 may depend on the cell type studied.