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1 Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, Alberta T6G 2P5; and 2 Department of Physiology and Lipid Research Unit, Laval University Hospital Research Center, Ste-Foy, Quebec, Canada G1V 4G2
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
9 M, maximal binding = 3.5 ± 0.23 × 1012 mol/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-
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-
, and all six cytokine receptor mRNA were induced by a mixture
of TNF-, IFN-, 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.
tumor necrosis factor-
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