AJP - Regulatory, Integrative and Comparative Physiology, Vol 270, Issue 1 145-R152, Copyright © 1996 by American Physiological Society
Effects of transforming growth factor-beta 1 on nitric oxide synthesis by C2C12 skeletal myocytes
G. Williams, L. Becker, D. Bryant, S. Willis and B. P. Giroir
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063, USA.
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.
