Inflammatory cytokines inhibit myogenic differentiation through activation of nuclear factor-kappaB

R.C.J. Langen, A.M.W.J. Schols, M.C.J.M. Kelders, E.F.M. Wouters, Y.M.W. Janssen-Heininger*

*Corresponding author for this work

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Inflammatory cytokines inhibit myogenic differentiation through activation of nuclear factor-kappaB.

Langen RC, Schols AM, Kelders MC, Wouters EF, Janssen-Heininger YM.

Department of Pulmonology, Maastricht University, Maastricht, The Netherlands.

Muscle wasting is often associated with chronic inflammation. Because tumor necrosis factor alpha (TNF-alpha) has been implicated as a major mediator of cachexia, its effects on C2C12 myocytes were examined. TNF-alpha activated nuclear factor-kappaB (NF-kappaB) and interfered with the expression of muscle proteins in differentiating myoblasts. Introduction of a mutant form of inhibitory protein kappaBalpha (IkappaBalpha) restored myogenic differentiation in myoblasts treated with TNF-alpha or interleukin 1beta. Conversely, activation of NF-kappaB by overexpression of IkappaB kinase was sufficient to block myogenesis, illustrating the causal link between NF-kappaB activation and inhibition of myogenic differentiation. The inhibitory effects of TNF-alpha on myogenic differentiation were reversible, indicating that the effects of the cytokine were not due to nonspecific toxicity. Treatment of differentiated myotubes with TNF-alpha did not result in a striking loss of muscle-specific proteins, which shows that myogenesis was selectively affected in the myoblast stage by TNF-alpha. An important finding was that NF-kappaB was activated to the same extent in differentiating and differentiated cells, illustrating that once myocytes have differentiated they become refractory to the effects of NF-kappaB activation. These results demonstrate that inflammatory cytokines may contribute to muscle wasting through the inhibition of myogenic differentiation via a NF-kappaB-dependent pathway
Original languageEnglish
Pages (from-to)1169-1180
Number of pages12
JournalFaseb Journal
Publication statusPublished - 1 Jan 2001

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