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Vol. 15, Issue 4, 2013-2026, April 2004
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B Activity Is Required for Skeletal Muscle Differentiation: Role of Interleukin-6
Center for Genomic Regulation, Program on Differentiation and Cancer, E-08003 Barcelona, Spain
Submitted August 12, 2003;
Revised December 30, 2003;
Accepted January 19, 2004
Monitoring Editor: Carl Henrik-Heldin
p38 MAPK and nuclear factor-
B (NF-B) signaling pathways have been implicated in the control of skeletal myogenesis. However, although 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 interleukin (IL)-6 expression is induced in C2C12 differentiating myoblasts, in a p38- and NF-B-dependent manner. Interference of IL-6 mRNA reduced, whereas 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 crosstalk between p38 MAPK and NF-B signaling pathways during myogenesis, with IL-6 being one of the effectors of this promyogenic mechanism.
* Corresponding author. E-mail address: pura.munoz{at}crg.es.
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