Abstract
Adult skeletal tissue is composed of heterogeneous population of cells that constantly self-renew by means of a controlled process of activation and proliferation of tissue-resident stem cells named satellite cells. Many growth factors, cytokines and myokines produced by skeletal muscle cells play critical roles in local regulation of the inflammatory process and skeletal muscle regeneration during different pathological conditions. IL-6 is a pleiotropic cytokine released in large amount during infection, autoimmunity and cancer. Low levels of IL-6 can promote activation of satellite cells and myotube regeneration while chronically elevated production promote skeletal muscle wasting. These distinct effects may be explained by a crosstalk of the IL-6/IL-6 receptor and gp130 trans-signaling pathway that oppose to regenerative and anti-inflammatory of the classical IL-6 receptor signaling pathway. Here we discuss on potential therapeutic strategies using monoclonal antibodies to IL-6R for the treatment of skeletal muscle wasting and cachexia. We also highlight on the IL-6/JAK/STAT and FGF/p38αβ MAPK signaling pathways in satellite cell activation and the use of protein kinase inhibitors for tailoring and optimizing satellite cell proliferation during the skeletal muscle renewal. Future investigations on the roles of the IL-6 classical and trans-signaling pathways in both immune and non-immune cells in skeletal muscle tissue will provide new basis for therapeutic approaches to reverse atrophy and degeneration of skeletal muscles in cancer and inflammatory diseases.
Highlights
Interleukin (IL)-6 is one of hundreds cytokines, chemokines and growth factors that function as mediators of the innate and adaptive immune responses (Pal et al 2014; Hunter and Jones 2015)
Acting at skeletal muscle tissue IL-6 may promote the proliferation of satellite cells and their incorporation as new myonuclei into existing fiber syncytia (Cantini et al 1995)
We will review emerging concepts and mechanisms that underlie the complex biology of IL-6 in regard to its roles in cancer cachexia and skeletal muscle renewal
Summary
Interleukin (IL)-6 is one of hundreds cytokines, chemokines and growth factors that function as mediators of the innate and adaptive immune responses (Pal et al 2014; Hunter and Jones 2015). The superfamily of IL-6 includes IL-6 itself, IL-11, IL-27, IL-31, leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), oncostatin M (OSM), cardiotropin-1 (CT-1), neuropoietin (NPN) and cardiotropin-like cytokine (CLC) (Lahiri et al 2001; Skiniotis et al 2008; Chalaris et al 2011) These cytokines and growth factors bind to specific receptors and activate a series of target genes involved in cell proliferation, cell differentiation, apoptosis and pro- and anti-inflammatory biochemical processes. Exercise increases IL‐6 synthesis by skeletal muscle cells Exercise is a complex process involving the synchronized and integrated activation of multiple tissues and organs, in particular, musculature, at the cellular and systemic level (Hawley et al 2014). Biochemical studies have supported the hypothesis that the degradation and release of 19S unit from the 26S large unit promote the entry of non-ubiquitinated substrates into 20S catalytic chamber for their rapid degradation (Takeuchi et al 2007; Belizario et al 2008)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
