Endotoxin Stimulates In Vivo Expression of Inflammatory Cytokines Tumor Necrosis Factor Alpha, Interleukin-1??, -6, and High-Mobility-Group Protein-1 in Skeletal Muscle

Abstract

The presence of increased levels of proinflammatory cytokines in the blood is associated with decreased muscle protein synthesis and the erosion of lean body mass in many catabolic conditions. However, little is known regarding the role of endogenous cytokine synthesis in muscle per se. The purpose of the present study was to characterize the cytokine expression profile of skeletal muscle in response to an in vivo injection of endotoxin (lipopolysaccharide, LPS). Intraperitoneal injection of a nonlethal dose of LPS (1,000 microg/kg Escherichia coli) into male rats increased the mRNA content of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta in gastrocnemius muscle as early as 1 h; IL-6 mRNA was not increased until 2 h post-LPS. Expression of TNF-alpha and IL-1beta peaked at 2 h (10- and 80-fold, respectively), whereas the increased IL-6 mRNA content (150-fold) peaked later at 4 h. The abundance of all measured cytokine mRNAs in skeletal muscle declined thereafter. The LPS-induced increase in muscle mRNA content for TNF-alpha, IL-6, and IL-1beta was dose-dependent with elevations being seen with as little as 10 microg/kg of LPS (2.5-, 8-, and 9-fold, respectively). In general, pretreatment of rats with dexamethasone attenuated but did not completely prevent the LPS-induced increase in muscle cytokine mRNA. LPS increased muscle TNF-alpha protein content approximately 2-fold and this increase was prevented by pretreatment with dexamethasone. LPS-induced increases in muscle IL-1beta and IL-6 protein were not detected. LPS also produced a 2-fold increase in the mRNA content of the high-mobility-group protein-1, a late-phase cytokine, in muscle at 12-24 h. Finally, although skeletal muscle was found to contain both the toll-like receptor (TLR)-2 and TLR4, LPS did not alter the mRNA content of TLR4 and produced a small (50%) but significant increase in TLR2 mRNA. These changes in TLRs were less dramatic than those observed for liver, spleen or cardiac muscle. Collectively these data indicate that skeletal muscle possesses many of the components of the innate immune system, including increases in both early- and late-phase cytokines and the presence of toll-like receptors.

L’ulcèrede Buruli

“…Premièrement, la mycolactone, en infiltrant progressivement le tissu musculaire, pourrait, au fur et à mesure qu'elle s'accumule, détruire les cellules inflammatoires recrutées dans le muscle squelettique agressé [5]. Le deuxième mécanisme repose sur l'observation que les cellules musculaires expriment des TLR (toll-like receptors) capables de reconnaître plusieurs variétés d'antigènes associés aux pathogènes [6,7]. Une fois agressées par les pathogènes, les cellules musculaires peuvent répondre et libérer des facteurs pro-inflammatoires et chimiotactiques tels que TNF-, IL-1 et IL-6 [6,7].…”

“…Le deuxième mécanisme repose sur l'observation que les cellules musculaires expriment des TLR (toll-like receptors) capables de reconnaître plusieurs variétés d'antigènes associés aux pathogènes [6,7]. Une fois agressées par les pathogènes, les cellules musculaires peuvent répondre et libérer des facteurs pro-inflammatoires et chimiotactiques tels que TNF-, IL-1 et IL-6 [6,7]. Ces facteurs pro-inflammatoires libérés activent les mastocytes résidents qui libéreront ensuite une panoplie de molécules immunorégulatrices telles que les interleukines (IL-3, 4, 5, 6, 9, 13),…”

Toll-like receptor 2 deficiency improves insulin sensitivity and hepatic insulin signalling in the mouse

“…Although the predominant site of TLR2 production is on cells of the innate immune system [17], TLR2 is found on a number of insulin-responsive cells, including adipose, skeletal muscle and liver cells [24,25]. However, the roles of TLR2 in initiating and maintaining inflammatoryassociated insulin resistance and energy homeostasis in vivo have not been established.…”

Exaggerated expression of skeletal muscle-derived interleukin-6, but not TNFα, in mice lacking interleukin-10

“…In response to LPS, skeletal muscle produces numerous cytokines including TNFα, IL-1β and IL-6 (Frost et al, 2002;Lang et al, 2003) which all have effects on muscle protein balance by affecting protein synthesis or degradation (Argiles et al, 2005;Frost and Lang, 2005). While TNFα and IL-1β display classic properties of pro-inflammatory cytokines, IL-6 has both proand anti-inflammatory properties (Tilg et al, 1997).…”