Contraction-induced Interleukin-6 Gene Transcription in Skeletal Muscle Is Regulated by c-Jun Terminal Kinase/Activator Protein-1

Whitham, Martin; Chan, Stanley M H; Pál, Martin; Matthews, Vance B.; Prelovsek, Oja; Lunke, Sebastian; El‐Osta, Assam; Broenneke, Hella; Alber, Jens; Brüning, Jens C.; Wunderlich, Frank; Lancaster, Graeme I.; Febbraio, Mark A.

doi:10.1074/jbc.m111.310581

Cited by 92 publications

(81 citation statements)

References 32 publications

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“…Evidence for this has been provided by a study showing that the NFκB signalling pathway is not activated after exercise and that binding of the p65 subunit of NFκB to the Il-6 promoter decreases with skeletal muscle contraction [14]. Results obtained in C2C12 myotubes and mice suggest that contraction-induced IL-6 expression is mediated by activation of c-Jun N-terminal kinase (JNK) and activator protein 1 (AP1) [14].…”

Section: Myokines and Metabolic Regulationmentioning

confidence: 76%

“…An important source of circulating IL-6 in obesity is the expanding visceral adipose tissue mass. Expression of IL-6 by macrophages within the adipose tissue is dependent on activation of the NFκB signalling pathway, whereas intramuscular IL-6 expression is regulated by different signalling cascades involving Ca 2+ , nuclear factor of activated T cells [83], calcineurin [84], p38 MAPK signalling [85] and JNK/AP1 [14]. These observations led investigators to question the functional role of IL-6 after exercise and in inflammatory conditions (reviewed in detail by Pedersen et al [13]).…”

Section: Myokines and Metabolic Regulationmentioning

confidence: 99%

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Myokines in insulin resistance and type 2 diabetes

et al. 2014

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Skeletal muscle represents the largest organ of the body in non-obese individuals and is now considered to be an active endocrine organ releasing a host of so-called myokines. These myokines are part of a complex network that mediates communication between muscle, the liver, adipose tissue, the brain and other organs. Recent data suggest that myokines regulated by muscle contraction may play a key role in mediating the health-promoting effects of regular physical activity. Although hundreds of myokines have recently been described in proteomic studies, we currently have a rather limited knowledge of the specific role these myokines play in the prevention of insulin resistance, inflammation and associated metabolic dysfunction. Several myokines are known to have both local and endocrine functions, but in many cases the contribution of physical activity to the systemic level of these molecules remains as yet unexplored. Very recently, novel myokines such as irisin, which is thought to induce a white to brown shift in adipocytes, have gained considerable interest as potential therapeutic targets. In this review, we summarise the most recent findings on the role of myokines in the regulation of substrate metabolism and insulin sensitivity. We further explore the role of myokines in the regulation of inflammation and provide a critical assessment of irisin and other myokines regarding their potential as therapeutic targets.

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Section: Myokines and Metabolic Regulationmentioning

confidence: 76%

Section: Myokines and Metabolic Regulationmentioning

confidence: 99%

Myokines in insulin resistance and type 2 diabetes

et al. 2014

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“…28 We previously reported that myogenesis response to muscle injury was blunted in IL-6 knockout mice, 29 which proved the positive effect of IL-6 on myogenesis. Other groups have also reported that electrical stimulation increases IL-6 in both cultured C2C12 cells 30 and human primary muscle cells. 31,32 In patients with CKD, Caglar et al 33 found that the increase in IL-6 concentration was modest during hemodialysis (14%) but that the levels increased dramatically at the end of the 2-hour posthemodialysis period (68% higher compared with baseline).…”

Section: Discussionmentioning

confidence: 99%

Low-Frequency Electrical Stimulation Attenuates Muscle Atrophy in CKD—A Potential Treatment Strategy

Klein

Hassounah

et al. 2015

Journal of the American Society of Nephrology

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Effective therapeutic strategies to treat CKD-induced muscle atrophy are urgently needed. Lowfrequency electrical stimulation (LFES) may be effective in preventing muscle atrophy, because LFES is an acupuncture technique that mimics resistance exercise by inducing muscle contraction. To test this hypothesis, we treated 5/6-nephrectomized mice (CKD mice) and control mice with LFES for 15 days. LFES prevented soleus and extensor digitorum longus muscle weight loss and loss of hind-limb muscle grip in CKD mice. LFES countered the CKD-induced decline in the IGF-1 signaling pathway and led to increases in markers of protein synthesis and myogenesis and improvement in muscle protein metabolism. In control mice, we observed an acute response phase immediately after LFES, during which the expression of inflammatory cytokines (IFN-g and IL-6) increased. Expression of the M1 macrophage marker IL-1b also increased acutely, but expression of the M2 marker arginase-1 increased 2 days after initiation of LFES, paralleling the change in IGF-1. In muscle cross-sections of LFES-treated mice, arginase-1 colocalized with IGF-1. Additionally, expression of microRNA-1 and -206, which inhibits IGF-1 translation, decreased in the acute response phase after LFES and increased at a later phase. We conclude that LFES ameliorates CKDinduced skeletal muscle atrophy by upregulation of the IGF-1 signaling pathway, which improves protein metabolism and promotes myogenesis. The upregulation of IGF-1 may be mediated by decreased expression of microRNA-1 and -206 and/or activation of M2 macrophages.

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“…Recently, we established an advanced in vitro muscle contraction model using cultured myotubes displaying vigorous EPSevoked contractile activity [17,18,21]. This model has increasingly been utilized by other researchers for investigating molecular mechanisms underlying various biological responses induced by actual contractile activity of muscle cells [24][25][26][27].…”

Section: Discussionmentioning

confidence: 99%