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Interleukin‐6 receptor expression in contracting human skeletal muscle: regulating role of IL‐6
Author(s) -
Keller Pernille,
Penkowa Milena,
Keller Charlotte,
Steensberg Adam,
Fischer Christian P.,
Giralt Mercedes,
Hidalgo Juan,
Pedersen Bente Klarlund
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-3278fje
Subject(s) - skeletal muscle , medicine , endocrinology , receptor , autocrine signalling , myokine , cytokine , glycoprotein 130 , biology , chemistry , interleukin 6
Contracting muscle fibers produce and release IL‐6, and plasma levels of this cytokine are markedly elevated in response to physical exercise. We recently showed autocrine regulation of IL‐6 in human skeletal muscle in vivo and hypothesized that this may involve up‐regulation of the IL‐6 receptor. Therefore, we investigated IL‐6 receptor regulation in response to exercise and IL‐6 infusion in humans. Furthermore, using IL‐6‐deficient mice, we investigated the role of IL‐6 in the IL‐6 receptor response to exercise. Human skeletal muscle biopsies were obtained in relation to: 3 h of bicycle exercise and rest ( n =6+5), or recombinant human IL‐6 infusion (rhIL‐6) or saline infusion ( n =6+6). We further obtained skeletal muscle samples from IL‐6 knockout (KO) mice and wild‐type C57/BL‐6 mice in response to a 1‐h bout of exercise. In exercising human skeletal muscle, IL‐6 receptor mRNA increased sixfold with a peak at 6 h postexercise. Detection of the IL‐6 receptor protein by immunohistochemistry revealed a pronounced staining following exercise that was primarily located at the cell membrane of the muscle fibers, whereas muscle gp130 expression and plasma levels of soluble IL‐6 receptor were unaffected. Infusion of rhIL‐6 to humans had no effect on the mRNA level of the IL‐6 receptor, whereas there was an increase at the protein level. IL‐6 receptor mRNA increased similarly in muscle of both IL‐6 KO mice and wild‐type mice in response to exercise. In conclusion, exercise increases IL‐6 receptor production in human skeletal muscle. This effect is most prominent 6 h after the end of the exercise bout, suggesting a postexercise‐sensitizing mechanism to IL‐6 when plasma IL‐6 is concomitantly low. Exercise‐induced increases in IL‐6 receptor mRNA most likely occurs via an IL‐6 independent mechanism as shown in IL‐6 KO mice and the human rhIL‐6 infusion study, whereas IL‐6 receptor protein levels are responsive to elevated plasma IL‐6 levels.