Cytokines and endotoxin induce cytokine receptors in skeletal muscle.
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 x 10(-9) M, maximal binding = 3.5+/-0.23 x 10(-12) 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-gamma receptor by RT-PCR, but these receptors were below limits of detection of ligand-binding assay (> or =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-alpha, and all six cytokine receptor mRNA were induced by a mixture of TNF-alpha, IFN-gamma, 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.
Zhang
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Y
Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, Alberta T6G 2P5.
Pilon
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G
Marette
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A
Baracos
V E
VE
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D019446:Endotoxemia / Q000378:metabolism; D004731:Endotoxins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018121:Receptors, Cytokine / Q000378:metabolism*; D017471:Receptors, Interferon / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology; D000096743:Interferon gamma Receptor
D016207:Cytokines; D004731:Endotoxins; D018121:Receptors, Cytokine; D017471:Receptors, Interferon; D017472:Receptors, Interleukin-1; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor