Involvement of Interleukin-6 in Activation of Lysosomal Cathepsin and Atrophy of Muscle Fibers Induced by Intramuscular Injection of Turpentine Oil in Mice

Abstract

Serum IL-6 level increased after the injection of turpentine oil into the right gastrocnemius muscle in mice. The mRNA level of IL-6 was highest in the injected muscle at 12 h after injection, but was not identified in the opposite muscle. The activities of cathepsins B and B+L started to elevate after 12 h in the injected muscle and markedly increased after day 3. Likewise, the mRNA levels of cathepsins B and L markedly increased from day 1 to day 5 in the injected muscle. However, a very mild increase was also observed in the opposite muscle. Immunohistochemical staining of cathepsins B and L exhibited positive reactions as fine granules in myofibers at 12 h and strong positive reactions in the infiltrating macrophages at 3 days. Atrophy of myofibers type 1 and 2 was evident in a time-dependent manner in the injected muscle. Treatment with rat anti-mouse IL-6 receptor monoclonal antibody inhibited the increase in cathepsin activities in the injected muscle. We conclude that IL-6 produced in the inflamed muscle is involved in the process of muscle degeneration, especially through the activation of lysosomal cathepsins.

Activity of lysosomal apparatus in rat myocardium during experimental coronary and noncoronary myocardial damage

“…This process may be considerably potentiated by LPO activation accompanying a drop in insulin synthesis [7], cytokine release (first of all, interleukin-6, which specifically activates B and D cathepsins [8]), and accumulation of oxidized LDL damaging lysosomes [11].…”

Complement Receptor 3 Promotes Severe Ross River Virus-Induced Disease

“…However, in contrast to what was found in that study, CR3 deficiency had no effect on RRV-induced expression of tumor necrosis factor alpha or IL-1␤. Interestingly, IL-6 induces skeletal muscle breakdown and the presence of IL-6 in inflamed muscle tissue contributes to skeletal muscle degeneration (53). In addition, IL-6 transgenic mice suffer skeletal muscle atrophy which can be reversed by treatment with IL-6 receptor antibody (51,52), suggesting that high levels of IL-6 within the diseased tissues may contribute to RRV pathogenesis.…”

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