title: Skeletal muscle wasting and renewal: a pivotal role of myokine IL-6.
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.
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Avenida Lineu Prestes, 1524, São Paulo, SP 05508-900 Brazil.
authors.forename: José E
authors.initials: JE
authors.lastname: Belizário
authors.affiliation: Unit of Muscle Biology, Lund University, BMC B12, 221 84 Lund, Sweden.
authors.forename: Cibely C
authors.initials: CC
authors.lastname: Fontes-Oliveira
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Avenida Lineu Prestes, 1524, São Paulo, SP 05508-900 Brazil.
authors.forename: Janaina Padua
authors.initials: JP
authors.lastname: Borges
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Avenida Lineu Prestes, 1524, São Paulo, SP 05508-900 Brazil.
authors.forename: Janete Akemi
authors.initials: JA
authors.lastname: Kashiabara
authors.affiliation: Division of Geographic Medicine and Infectious Disease, Tufts Medical Center, Boston, MA 02111 USA.
authors.forename: Edouard
authors.initials: E
authors.lastname: Vannier
keywords: Anti-IL-6 receptor monoclonal antibodies; Cancer cachexia; Exercise; IL-6; IL-6/IL-6R/gp130 signaling pathway; Jak/STAT signaling; Satellite cells; Skeletal muscle