Lipopolysaccharide regulates proinflammatory cytokine expression in mouse myoblasts and skeletal muscle.
The purpose of the present study was to examine the regulation of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 by lipopolysaccharide (LPS) in C2C12 myoblasts and mouse skeletal muscle. LPS produced dose- and time-dependent increases in TNF-alpha and IL-6 mRNA content in C2C12 myoblasts. The LPS-induced cytokine response could be mimicked by peptidoglycan from the cell wall of Staphylococcus aureus but not by zymosan A, a cell wall component from Saccharomyces cerevisiae. Ongoing protein synthesis was not necessary for the increase in the two cytokine mRNAs. The transcriptional inhibitor 5,6-dichloro-beta-D-ribofuranosyl-benzimidazole blocked LPS-stimulated IL-6 mRNA expression without changing its mRNA half-life. The anti-inflammatory glucocorticoid dexamethasone selectively blocked LPS-stimulated IL-6 mRNA accumulation but not TNF-alpha. In contrast, the proteasomal inhibitor MG-132 blocked TNF-alpha mRNA expression but not IL-6. Exposure of myoblasts to LPS was associated with a rapid decrease in the inhibitor of nuclear factor-kappaB (I kappaB, alpha, and epsilon), and this response was also blocked by MG-132. Treatment of myocytes with IL-1 or TNF-alpha also increased IL-6 mRNA content, but the increase in IL-6 mRNA due to LPS could not be prevented by pretreatment with antagonists to either IL-1 or TNF. Under in vivo conditions, LPS increased the plasma concentration of TNF-alpha and IL-6 and stimulated the accumulation of their mRNAs in multiple tissues including skeletal muscle from wild-type mice. In contrast, the ability of LPS to stimulate the same cytokines was markedly decreased in mice that harbor a mutation in the Toll-like receptor 4. Our data suggest that LPS stimulates cytokine expression not only in classical immune tissues but also in skeletal muscle.[1]References
- Lipopolysaccharide regulates proinflammatory cytokine expression in mouse myoblasts and skeletal muscle. Frost, R.A., Nystrom, G.J., Lang, C.H. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2002) [Pubmed]
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