Systemic IL-6 regulation of eccentric contraction-induced muscle protein synthesis

Justin P. Hardee, Dennis K. Fix, Xuewen Wang, Edie C. Goldsmith, Ho Jin Koh, James Carson

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Systemic cytokines and contractile activity are established regulators of muscle protein turnover. Paradoxically, the IL-6 cytokine family, which shares the ubiquitously expressed membrane gp130 receptor, has been implicated in skeletal muscle’s response to both contractions and cancer-induced wasting. Although we have reported that tumorderived cachectic factors could suppress stretch-induced protein synthesis in cultured myotubes, the ability of systemic cytokines to disrupt in vivo eccentric contraction-induced protein synthesis has not been established. Therefore, we examined whether systemic IL-6 regulates basal and eccentric contraction-induced protein synthesis through muscle gp130 signaling. Systemic IL-6 overexpression was performed for 2 wk, and we then examined basal and eccentric contraction-induced protein synthesis and mammalian target of rapamycin complex 1 (mTORC1) signaling in tibialis anterior muscle of male wild-type, muscle-specific gp130 receptor knockout, and tumorbearing ApcMin/+ mice. Systemic IL-6 overexpression suppressed basal protein synthesis and mTORC1 signaling independently of IL-6 level, which was rescued by muscle gp130 loss. Interestingly, only high systemic IL-6 levels suppressed eccentric contraction-induced protein synthesis. Systemic IL-6 overexpression in precachectic tumor- bearing ApcMin/+ mice accelerated cachexia development, which coincided with suppressed basal and eccentric contraction-induced muscle protein synthesis. The suppression of eccentric contractioninduced protein synthesis by IL-6 occurred independently of mTORC1 activation. Collectively, these findings demonstrate that basal protein synthesis suppression was more sensitive to circulating IL-6 compared with the induction of protein synthesis by eccentric contraction. However, systemic IL-6 can interact with the cancer environment to suppress eccentric contraction-induced protein synthesis independently of mTORC1 activation.

Original languageEnglish (US)
Pages (from-to)C91-C103
JournalAmerican Journal of Physiology - Cell Physiology
Volume315
Issue number1
DOIs
StatePublished - Jul 1 2018

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Muscle Proteins
Interleukin-6
Proteins
Muscles
Cytokines
Neoplasms
Cachexia
Skeletal Muscle Fibers
Skeletal Muscle
Membranes
mechanistic target of rapamycin complex 1

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

Cite this

Systemic IL-6 regulation of eccentric contraction-induced muscle protein synthesis. / Hardee, Justin P.; Fix, Dennis K.; Wang, Xuewen; Goldsmith, Edie C.; Koh, Ho Jin; Carson, James.

In: American Journal of Physiology - Cell Physiology, Vol. 315, No. 1, 01.07.2018, p. C91-C103.

Research output: Contribution to journalArticle

Hardee, Justin P. ; Fix, Dennis K. ; Wang, Xuewen ; Goldsmith, Edie C. ; Koh, Ho Jin ; Carson, James. / Systemic IL-6 regulation of eccentric contraction-induced muscle protein synthesis. In: American Journal of Physiology - Cell Physiology. 2018 ; Vol. 315, No. 1. pp. C91-C103.
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