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Inhibitory effects of IL‐6 on IGF‐1 activity in skeletal myoblasts could be mediated by the activation of SOCS‐3
Author(s) -
AlShanti Nasser,
Stewart Claire E.
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23420
Subject(s) - myogenin , skeletal muscle , myod , medicine , endocrinology , myocyte , insulin like growth factor , biology , growth factor , protein kinase b , myostatin , myogenesis , phosphorylation , microbiology and biotechnology , receptor
In elderly people, low and high levels of insulin‐like growth factor 1 (IGF‐1) and interleukin‐6 (IL‐6), respectively, are well documented and may contribute to reduced muscle mass and poor muscle function of ageing and suggesting a biological interactions between IGF‐1 and IL‐6. However, the dual effect of IGF‐1/IL‐6 on skeletal muscle differentiation and proliferation has not been fully investigated. We therefore hypothesised that IL‐6 impairs the biological activity of IGF‐1 in skeletal muscle through inhibiting its signalling pathways, ERK1/2 and Akt. Our aim was to examine the combined effects of these factors on models of muscle wasting, with objectives to examine skeletal muscle differentiation and proliferation using the murine C2 skeletal muscle cell line. Cells were cultured with DM, IGF‐1 and IL‐6 alone (control treatments), or co‐cultured with IGF‐1/IL‐6. Co‐incubation of C2 cells in IGF‐1 plus IL‐6 resulted in maximal cell death (22 ± 4%; P < 0.005) compared with control treatments (14 ± 2.9%). This was also confirmed by cyclin D1 expression levels in co‐incubation treatments (7 ± 3.5%; P < 0.05) compared with control treatments (∼23%). The expression levels of myogenic‐specific transcriptional factor mRNAs (myoD and myogenin) were also significantly ( P < 0.005) reduced by 70% and 90%, respectively, under the co‐incubation regimes, compared with control treatments. Signalling investigations showed significant phosphorylation reduction by 20%, ( P < 0.05) of ERK1/2 and Akt in co‐incubation treatments relative to either treatment alone. Expression studies for SOCS‐3 (1.6‐fold ± 0.08, P < 0.05) and IRS‐1 (0.65‐fold ± 0.13 P < 0.005) mRNAs showed significant elevation and reduction for both genes, respectively, in co‐treatments relative to control treatments. These data may suggest that IL‐6 exerts its inhibitory effects on IGF‐1 signalling pathways (ERK1/2 and Akt) through blocking its receptor substrate IRS‐1 by SOCS‐3. J. Cell. Biochem. 113: 923–933, 2012. © 2011 Wiley Periodicals, Inc.