Regulation of G-CSF and its receptor in skeletal muscle in response to exercise-induced damage in vivo and LPS stimulation in vitro (#200)
The cytokine granulocyte-colony stimulating factor (G-CSF) binds to its receptor (G-CSFR) to stimulate haematopoietic stem cell mobilization, myelopoiesis and the production and activation of neutrophils. G-CSF is increased in the circulation in response to exercise-induced muscle damage and the G-CSF receptor (G-CSFR) has recently been identified in skeletal muscle and muscle cells1. While G-CSF/G-CSFR activation mediates pro- and anti-inflammatory responses, our understanding of their role and regulation in skeletal muscle is limited. The aim of this study was to investigate in vitro and in vivo the role and regulation of G-CSF and the G-CSFR in skeletal muscle under conditions of muscle inflammation and damage. Firstly, C2C12 myotubes were treated with G-CSF to determine if it modulates the inflammatory response induced by lipopolysaccharide (LPS). Secondly, we measured the regulation of G-CSF and its receptor following eccentric exercise-induced muscle damage and investigated if their expression levels were redox-dependent by administering the antioxidant N-AcetylCysteine. LPS stimulation of C2C12 myotubes resulted in G-CSF production. The addition of G-CSF following LPS stimulation of C2C12 myotubes increased IL-6 mRNA and cytokine release into the media. Following eccentric exercise-induced muscle damage in humans G-CSF levels were either marginally increased in circulation or remain unaltered in skeletal muscle. Similarly, G-CSFR levels remained unchanged in response to damaging exercise while the G-CSF/G-CSFR response was not redox sensitive. Collectively, these findings suggest that G-CSF may cooperate with IL-6 and potentially promote muscle regeneration in vitro, whereas in vivo aseptic inflammation induced by exercise did not change G-CSF and G-CSFR responses. These observations suggest that different models of inflammation produce a different G-CSF responses.
- 1. Wright CR, Brown EL, Della Gatta PA, Ward AC, Lynch GS, and Russell AP. G-CSF does not influence C2C12 myogenesis despite receptor expression in healthy and dystrophic skeletal muscle. Front Physiol 5: 175, 2014.