Proinflammatory cytokines are important factors in the regulation of diverse aspects of skeletal muscle function; however, the muscle cytokine receptors mediating these functions are uncharacterized. Binding kinetics (dissociation constant = 39 ± 4.7 × 10−9M, maximal binding = 3.5 ± 0.23 × 10−12mol/mg membrane protein) of muscle tumor necrosis factor (TNF) receptors were obtained. Skeletal muscle was found to express mRNAs encoding interleukin-1 type I and II receptors, interleukin-6 receptor (IL-6R), and interferon-γ receptor by RT-PCR, but these receptors were below limits of detection of ligand-binding assay (≥1 fmol binding sites/mg protein). Twenty-four hours after intraperitoneal administration of endotoxin to rats, TNF receptor type II (TNFRII) and IL-6R mRNA were increased in skeletal muscle ( P < 0.05). In cultured L6 cells, the expression of mRNA encoding TNFRII and IL-6R receptors was induced by TNF-α, and all six cytokine receptor mRNA were induced by a mixture of TNF-α, IFN-γ, and endotoxin ( P < 0.05). This suggests that the low level of cytokine receptor expression is complemented by a capacity for receptor induction, providing a clear mechanism for amplification of cytokine responses at the muscle level.
Interferon-γ is a master checkpoint regulator of cytokine-induced differentiation
