TLR4-defective (C3H/HeJ) mice are not protected from cast immobilization-induced muscle atrophy

Abstract

Recent studies have shown that activation of Toll-like receptor (TLR)4 signaling may be an important factor in muscle atrophy and excessive inflammatory response associated with immobilization. To examine the role of TLR4 signaling on cast immobilization-induced skeletal muscle atrophy, we tested the hypothesis that muscle atrophy and inflammation after cast immobilization is reduced in TLR4-defective mice. TLR4-defective (C3H/HeJ) and wild type (C3H/HeN) mice were divided into control and cast-immobilization groups. Cast immobilization was imposed for 14 days. Cast immobilization increased TLR4 mRNA expression in the gastrocnemius and decreased muscle mass and cross-sectional area (CSA) of the gastrocnemius fibers. However, there was no difference in the gastrocnemius muscle mass and CSA between TLR4-defective and wild type mice. Cast immobilization-induced increase in ubiquitin E3 ligases (MAFbx/Atrogin-1 and MuRF1), inflammatory cytokines, and macrophage/monocyte marker mRNAs were unaffected by defective TLR4. Our findings in C3H/HeJ mice suggested that TLR4 signaling might not play an essential role in immobilization-induced muscle atrophy.