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Skeletal Muscle as an Endocrine organ; the effect of TNF‐alpha
Author(s) -
Lightfoot Adam Paul,
Harrison Dawn,
Kayani Anna,
McArdle Francis,
Griffiths Richard D,
McArdle Anne
Publication year - 2010
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/fasebj.24.1_supplement.816.3
Subject(s) - myogenesis , tumor necrosis factor alpha , endocrinology , cytokine , medicine , skeletal muscle , proinflammatory cytokine , paracrine signalling , myokine , inflammation , chemistry , in vivo , biology , receptor , microbiology and biotechnology
During chronic inflammation muscle is exposed to inflammatory cytokines; a key player in this is TNF‐α. Muscle has protective mechanisms to adapt to stress, via further expression of cytokines and Heat shock proteins (HSPs), which can be released into the extracellular environment and then involved in apocrine or paracrine signalling pathways. C2C12 myotubes in vitro treated with TNF‐α (25ng/ml) showed significant up‐regulation of 7 pro‐inflammatory genes by qPCR array analysis. Significant release of cytokines (IL‐6, MCP‐1, KC, IP‐10 & RANTES) was seen after 3 & 6 hours. In addition, TNF‐α up‐regulated intracellular levels of HSP60 & 70, with specific release of HSP60 at 3 hours. Treatment of C2C12 myotubes with recombinant HSP60 and 70 induced significant release of MCP‐1 and RANTES at 3 hours. Adult and old C57Bl6 mice treated with TNF‐α (7.5μg/kg) i.v. were subject to microdialysis perfusion of the gastrocnemius muscle to measure direct cytokine release from whole muscle. Adult mice showed a significant release of IL‐1β & MCP‐1, 1 hour post TNF‐α; old mice showed elevated basal levels of IL‐1β & MCP‐1, with a blunted response to TNF‐α. Data show TNF‐α induces an immune and stress response in muscle in vitro and HSPs have a paracrine signalling effect inducing release of cytokines. Whole muscle in vivo releases cytokines in response to TNF‐α treatment which is blunted in old mice. Supported by University of Liverpool.