Mesenchymal Stem Cells Alter the Inflammatory Response of C2C12 Mouse Skeletal Muscle Cells

Biol Pharm Bull. 2020;43(11):1785-1791. doi: 10.1248/bpb.b20-00536.


Mesenchymal stem cells (MSCs) are capable of repairing skeletal muscle via paracrine mechanisms. This regenerative effect of MSCs on skeletal muscle is based on promoting the proliferation and differentiation of myogenic cells and inhibiting the inflammatory response of immune cells. However, it is unclear whether MSCs affect the inflammatory response of skeletal muscle cells. In this study, we evaluated the paracrine effect of mouse MSCs on the inflammatory response of lipopolysaccharide (LPS)-stimulated C2C12 mouse myoblasts. Interleukin (IL)-6 production from LPS-stimulated C2C12 cells was significantly increased by coculture with MSCs or culture in conditioned medium of MSCs. This increased IL-6 production from C2C12 cells was not significantly suppressed by inhibiting mitogen-activated protein kinase pathways, but it was significantly suppressed by pretreatment with nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) inhibitors. In addition, IL-6 and inducible nitric oxide synthase (iNOS) mRNA expression was increased significantly in C2C12 cells cocultured with MSCs, while tumor necrosis factor (TNF)-α and IL-1β mRNA expression was decreased. Furthermore, conditioned medium of C2C12 cells cocultured with MSCs exerted remarkable anti-inflammatory effects on LPS-stimulated mouse macrophages.

Keywords: inflammatory response; interleukin (IL)-6; mesenchymal stem cell; skeletal muscle.

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Cell Line
  • Cell Proliferation
  • Coculture Techniques
  • Culture Media, Conditioned / metabolism
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / immunology
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / immunology*
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Myoblasts, Skeletal / immunology*
  • Myoblasts, Skeletal / metabolism
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Paracrine Communication / immunology*
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • Culture Media, Conditioned
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Tnf protein, mouse
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse