{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:36:21Z","timestamp":1790775381687,"version":"4.1.0"},"reference-count":53,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA-121249"],"award-info":[{"award-number":["R01 CA-121249"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["P20 RR-017698"],"award-info":[{"award-number":["P20 RR-017698"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2018,7,1]]},"abstract":"<jats:p> 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\u2019s response to both contractions and cancer-induced wasting. Although we have reported that tumor-derived 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 tumor-bearing Apc<jats:sup>Min\/+<\/jats:sup> 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 Apc<jats:sup>Min\/+<\/jats:sup> mice accelerated cachexia development, which coincided with suppressed basal and eccentric contraction-induced muscle protein synthesis. The suppression of eccentric contraction-induced 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. <\/jats:p>","DOI":"10.1152\/ajpcell.00063.2018","type":"journal-article","created":{"date-parts":[[2018,4,11]],"date-time":"2018-04-11T20:10:28Z","timestamp":1523477428000},"page":"C91-C103","source":"Crossref","is-referenced-by-count":24,"title":["Systemic IL-6 regulation of eccentric contraction-induced muscle protein synthesis"],"prefix":"10.1152","volume":"315","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6469-9592","authenticated-orcid":false,"given":"Justin P.","family":"Hardee","sequence":"first","affiliation":[{"name":"Department of Exercise Science, University of South Carolina, Columbia, South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis K.","family":"Fix","sequence":"additional","affiliation":[{"name":"Department of Exercise Science, University of South Carolina, Columbia, 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