Gene Expression of Receptors for IL-6, LIF, and CNTF in Regenerating Skeletal Muscles

Abstract

The biological actions of interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and ciliary neurotrophic factor (CNTF) are mediated via respective functional receptor complexes consisting of a common signal-transducing component, gp130, and other specific receptor components, IL-6 receptor α (IL-6R), LIF receptor β (LIFR), and CNTF receptor α (CNTFR). IL-6, LIF, and CNTF are implicated in skeletal muscle regeneration. However, the cell populations that express these receptor components in regenerating muscles are unknown. Using in situ hybridization histochemistry, we examined spatiotemporal expression patterns of gp130, IL-6R, LIFR, and CNTFR mRNAs in regenerating muscles after muscle contusion. At the early stages of regeneration (from 3 hr to Day 2 post contusion), significant signals for gp130 and LIFR mRNAs were detected in myonuclei and/or nuclei of muscle precursor cells (mpcs) and in mononuclear cells located in extracellular spaces between myofibers after muscle contusion, but IL-6R mRNA was expressed only in mononuclear cells. At Day 7 post contusion, signals for gp130, LIFR, and IL-6R mRNAs were not detected in newly formed myotubes, whereas the CNTFR mRNA level was upregulated in myotubes. These findings suggest that the upregulation of receptor subunits in distinct cell populations plays an important role in the effective regeneration of both myofibers and motor neurons.

Chronic Exposure to Interleukin-6 Causes Hepatic Insulin Resistance in Mice

“…These results suggest that IL-6 may not play a role in mediating insulin resistance in skeletal muscle. This agrees with reports indicating exceedingly low levels of IL-6 receptors expressed in muscle cells (36,37). Alternatively, the concentrations of IL-6 used in our current study may be too low to elicit a response in skeletal muscle.…”

Oncostatin M inhibits myoblast differentiation and regulates muscle regeneration

“…Two major intracellular signal transduction pathways, namely the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and the extracellular signal-regulated kinase (ERK) pathways, are known to mediate most of the biological effects of the IL-6-type cytokines [28]. During the injury-induced muscle regeneration, it has been shown that the mRNAs for IL-6, LIF, gp130, and LIFR are quickly induced on injury [29][30][31]. However, the role of OSM in myoblast differentiation and muscle regeneration remains unexplored.…”

Interleukin-6/Signal Transducer and Activator of Transcription 3 (STAT3) Pathway Is Essential for Macrophage Infiltration and Myoblast Proliferation during Muscle Regeneration

“…Among the cytokines secreted by proinflammatory macrophages, significantly increased expression of IL-6 and IL-6R mRNA was first seen in the injury site at 3 h after cardiotoxin injury (11,12). Exogenous recombination IL-6 influence the proliferation and differentiation of cultured myoblast derived from human or mouse muscle.…”