| First Author | Frost RA | Year | 2002 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 283 |
| Issue | 3 | Pages | R698-709 |
| PubMed ID | 12185005 | Mgi Jnum | J:78901 |
| Mgi Id | MGI:2386463 | Doi | 10.1152/ajpregu.00039.2002 |
| Citation | Frost RA, et al. (2002) Lipopolysaccharide regulates proinflammatory cytokine expression in mouse myoblasts and skeletal muscle. Am J Physiol Regul Integr Comp Physiol 283(3):R698-709 |
| abstractText | 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. |
