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Suppressor of cytokine signaling‐3 (SOCS‐3) expression contributes to increases in interleukin‐6 (IL‐6) expression after exercise training.
Author(s) -
Spangenburg Espen E,
Brown David A,
Johnson Micah S,
Kearney Brittany,
Pettycrew Emily,
Moore Russell L
Publication year - 2006
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.20.4.a390-a
Subject(s) - luciferase , myogenesis , skeletal muscle , soleus muscle , gene expression , biology , transfection , microbiology and biotechnology , endocrinology , medicine , chemistry , gene , biochemistry
We recently demonstrated that SOCS‐3 is expressed in skeletal muscle. Thus, we examined the effects of exercise training on SOCS‐3 expression in skeletal muscle and the potential role of SOCS‐3 in muscle. Female Sprague‐Dawley Rats (5–8 mos) were treadmill trained everyday for 12 weeks, resulting in a 62% increase in citrate synthase activity in the plantaris muscle. Exercise training increased SOCS‐3 mRNA expression by 80% and 154% in the plantaris and soleus muscle, respectively. To mimic the effects of increased SOCS‐3 expression, SOCS‐3 cDNA was co‐transfected with a NF‐kappa beta luciferase construct into cultured myotubes. SOCS‐3 overexpression increased NF‐ kappa beta transcriptional activity by 27‐fold. The proximal region of the IL‐6 gene promoter contains a NF‐ kappa beta consensus site, which contributes to increased IL‐6 expression in various tissues. We attempted to determine if SOCS‐3 induced IL‐6 transcription though activation of this consensus site. SOCS‐3 cDNA was co‐transfected into cultured myotubes with either the IL‐6 luciferase construct or a mutated NF‐ kappa beta IL‐6 luciferase construct. SOCS‐3 overexpression increased IL‐6 transcriptional activity by 15‐fold, however when the NF‐ kappa beta site was mutated SOCS‐3 failed to increase IL‐6 transcriptional activity. We subsequently found that IL‐6 mRNA expression was elevated in the plantaris and soleus muscles of the trained animals compared to the sedentary animals. These data suggest that training‐induced elevations in SOCS‐3 expression in skeletal muscle may contribute to the exercise‐induced increase in IL‐6 expression through activation of NF‐ kappa beta. Supported by NIH HL 40306‐15 and HL 72790‐02 (RLM).