Tsujinaka T, Kishibuchi M, Yano M, Morimoto T, Ebisui C, Fujita J, Ogawa A, Shiozaki H, Kominami E, Monden M
Department of Surgery II, Osaka University Medical School, Suita.
J Biochem. 1997 Sep;122(3):595-600. doi: 10.1093/oxfordjournals.jbchem.a021794.
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.
给小鼠右腓肠肌注射松节油后，血清白细胞介素-6（IL-6）水平升高。注射后12小时，注射肌肉中IL-6的mRNA水平最高，但在对侧肌肉中未检测到。注射后12小时，注射肌肉中组织蛋白酶B和B+L的活性开始升高，3天后显著增加。同样，注射肌肉中组织蛋白酶B和L的mRNA水平从第1天到第5天显著增加。然而，在对侧肌肉中也观察到非常轻微的增加。组织蛋白酶B和L的免疫组织化学染色在12小时时在肌纤维中呈细颗粒状阳性反应，在3天时在浸润的巨噬细胞中呈强阳性反应。注射肌肉中1型和2型肌纤维萎缩呈时间依赖性明显。用大鼠抗小鼠IL-6受体单克隆抗体治疗可抑制注射肌肉中组织蛋白酶活性的增加。我们得出结论，炎症肌肉中产生的IL-6参与肌肉退化过程，尤其是通过溶酶体组织蛋白酶的激活。
