Stimulated myotube contractions regulate membrane-bound and soluble TLR4 to prevent LPS-induced signaling and myotube atrophy in skeletal muscle cells

Abstract

Excessive Toll-like receptor 4 (TLR4) activation causes muscle atrophy. Muscle contractions can limit TLR4 activation on immune cells, but its impact on TLR4 expressed on skeletal muscle cells remains unclear. Here, we demonstrate in C2C12 myotubes for the first time that stimulated myotube contractions reduce membrane-bound TLR4 and increase soluble TLR4, preventing TLR4-mediated signaling and myotube atrophy. Further analyses revealed soluble TLR4 independently prevents myotube atrophy, supporting a potential therapeutic role in combating TLR4-mediated atrophy.