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Cytokines and endotoxin induce cytokine receptors in skeletal muscle

作者:Yan Zhang, Geneviève Pilon, André Marette, Vickie Elaine Baracos · 发表于:American Journal of Physiology-Endocrinology and Metabolism · 年份:2000 · DOI:10.1152/ajpendo.2000.279.1.e196 · 被引用次数:94 · 研究领域:Exercise and Physiological Responses、Adipose Tissue and Metabolism、Adipokines, Inflammation, and Metabolic Diseases

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.