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Anti‐inflammatory Cytokine Receptor Prevents Muscle Atrophy
Author(s) -
Kwon YoungWon,
Son Young Hoon,
Park SunDong,
Lee JuHee
Publication year - 2017
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.31.1_supplement.lb779
Subject(s) - skeletal muscle , myogenesis , cytokine , endocrinology , medicine , proinflammatory cytokine , inflammation , muscle atrophy , cachexia , protein kinase b , tumor necrosis factor alpha , atrophy , myocyte , biology , signal transduction , microbiology and biotechnology , cancer
Skeletal muscle plays a leading role in the metabolism and concurrently functions as a repository of protein and amino acids. In many serious diseases such as cancer cachexia and sepsis, excessive secretion of cytokines exacerbates skeletal muscle wasting and metabolic imbalance. Excessively increased cytokines due to disease and tissue damage are regulated by anti‐inflammatory cytokines. However, the precise mechanisms of anti‐inflammatory cytokine in skeletal muscle atrophy have not been fully elucidated. Interleukin‐10 (IL‐10) is an anti‐inflammatory cytokine that improved insulin resistance in high fat diet and aging. The physiological effects of IL‐10 in skeletal muscle were known, but the study of IL‐10 receptor (IL‐10R) was unknown. Our hypothesis was that IL‐10R regulates muscle atrophy in vitro model. In our study, we found that IL‐10 mRNA levels were significantly elevated in various muscle atrophy conditions including the treatment of H 2 O 2 , dexamethasone, and cancer cell conditioned media. This is the regulation for suppressing the pro‐inflammatory cytokine, but the mechanism of IL‐10R is unidentified. In order to confirm the directly role of IL‐10R in skeletal muscle, we used the IL‐10R siRNA in C2C12 myotubes. Knockdown of IL‐10R increased the protein level of Atrogin‐1 by Foxo dependent activation, but MuRF1 level by NF‐κB dependent activation remained unchanged. Increased Atrogin‐1 is associated with the reduction of Akt signaling. Declining Akt activity leads to decrease in overall protein synthesis. Using puromycin incorporation, we proved that suppression of IL‐10R reduced the protein synthesis in myotubes. As a result, inhibition of IL‐10R implies a deficit of protein synthesis due to reducing Akt activation. According to our data, the inhibition of IL‐10R is caused by activation of E3 ligase via inhibition of insulin signaling. Our findings suggest that activation of IL‐10R may exert the potential therapeutic effect of skeletal muscle atrophy. Support or Funding Information This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Education) (No.2015R1D1A1A01060340).