Adhikari Abhinav, Cobb Brittan, Eddington Seth, Becerra Nathalie, Kohli Punit, Pond Amber, Davie Judith
Department of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, IL, USA.
Department of Anatomy, Southern Illinois University School of Medicine, Carbondale, IL, USA.
Cytokine X. 2020 Apr 8;2(2):100023. doi: 10.1016/j.cytox.2020.100023. eCollection 2020 Jun.
Interleukin 6 (IL-6) is a secreted cytokine that is an important mediator of the immune response in numerous tissues, including skeletal muscle. IL-6 is considered a myokine as it can be secreted by muscle. IL-6 is secreted following exercise, where it exerts both pro-myogenic effects as well as anti-myogenic effects such as promoting atrophy and muscle wasting. The regulation of IL-6 in skeletal muscle is not well understood. The purpose of this study was to determine if IFN-γ and TNF-ɑ stimulate IL-6 in skeletal muscle. We found that both IFN-γ and TNF-α stimulate IL-6 in skeletal muscle, but the stimulation is not cooperative as seen in monocytes. We have previously shown that the IFN-γ stimulated class II major histocompatibility complex transactivator (CIITA) mediates many of the effects of IFN-γ in skeletal muscle and we show here that CIITA directly stimulates IL-6. The regulation of IL-6 by CIITA is clearly complex, as we found that CIITA both stimulates and restrains IL-6 expression. To show that these effects could be observed in a physiological setting, mice were treated with IFN-γ and we found that both CIITA and IL-6 were upregulated in skeletal muscle.
白细胞介素6（IL-6）是一种分泌型细胞因子，是包括骨骼肌在内的许多组织中免疫反应的重要介质。IL-6被认为是一种肌动蛋白，因为它可以由肌肉分泌。运动后会分泌IL-6，它既具有促肌生成作用，也具有抗肌生成作用，如促进萎缩和肌肉消耗。骨骼肌中IL-6的调节机制尚不清楚。本研究的目的是确定IFN-γ和TNF-α是否刺激骨骼肌中的IL-6。我们发现IFN-γ和TNF-α都能刺激骨骼肌中的IL-6，但这种刺激不像在单核细胞中那样具有协同作用。我们之前已经表明，IFN-γ刺激的II类主要组织相容性复合体反式激活因子（CIITA）介导了IFN-γ在骨骼肌中的许多作用，我们在此表明CIITA直接刺激IL-6。CIITA对IL-6的调节显然很复杂，因为我们发现CIITA既能刺激也能抑制IL-6的表达。为了证明这些效应可以在生理环境中观察到，用IFN-γ处理小鼠，我们发现骨骼肌中CIITA和IL-6都上调了。
