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A more recent version of this article appeared on April 1, 2004
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Submitted on August 12, 2003
Revised on December 30, 2003
Accepted on January 19, 2004
B activity is required for skeletal muscle differentiation: role of IL-6
1 Center for Genomic Regulation (CRG), Program on Differentiation and Cancer, Barcelona, Spain
* Corresponding author. E-mail address: pura.munoz{at}crg.es.
p38 MAPK and NF-
B signaling pathways have been implicated in the control of skeletal myogenesis. However, while p38 is recognized as a potent activator of myoblast differentiation, the role of NF-B remains controversial. Here, we show that p38 is activated only in differentiating myocytes, whereas NF-B activity is present both in proliferation and differentiation stages. NF-B activation was found to be dependent on p38 activity during differentiation, being NF-B an effector of p38, thus providing a novel mechanism for the promyogenic effect of p38. Activation of p38 in C2C12 cells induced the activity of NF-B, in a dual way: first, by reducing IB
levels and inducing NF-B-DNA-binding activity and, second, by potentiating the transactivating activity of p65- NF-B. Finally, we show that IL-6 expression is induced in C2C12 differentiating myoblasts, in a p38- and NF-B-dependent manner. Interference of IL-6 mRNA reduced, while its overexpression increased, the extent of myogenic differentiation; moreover, addition of IL-6 was able to rescue significantly the negative effect of NF-B inhibition on this process. This study provides the first evidence of a cross-talk between p38 MAPK and NF-B signaling pathways during myogenesis, with IL-6 being one of the effectors of this promyogenic mechanism.
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