Effects of transforming growth factor-[beta]1 on nitric oxide
synthesis by c2c12 skeletal myocytes.
Williams, Gary, Lisa Becker, Debbie Bryant, Susan Willis, and Brett P.
Giroir.
The Laboratories for Molecular Biology and Physiology Research, The
Department of Pediatrics, The University of Texas Southwestern
Medical Center, Dallas, Texas
APStracts 2:0207R, 1995.
The production of nitric oxide (NO) via the inducible form of nitric
oxide 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
suggests that the regulation of NO production by TGF-[beta]1 may
depend on the cell type studied.
Received 6 October 1994; accepted in final form 18 July 1995.
APS Manuscript Number R581-4.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.