IL-1β and TNF-α Modulation of Proliferated and Committed Myoblasts: IL-6 and COX-2-Derived Prostaglandins as Key Actors in the Mechanisms Involved.
IL-1β and TNF-α Modulation of Proliferated and Committed Myoblasts: IL-6 and COX-2-Derived Prostaglandins as Key Actors in the Mechanisms Involved.
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DOI：
10.3390/cells9092005
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发表时间：
2020-09-01
期刊：
影响因子：
6
通讯作者：
Moreira V
中科院分区：
文献类型：
--
作者：
Alvarez AM;DeOcesano-Pereira C;Teixeira C;Moreira V
本研究旨在探讨促炎细胞因子IL-1β和TNF-α对成肌细胞增殖和定向分化的影响及其机制。培养C2 C12小鼠成肌细胞以达到增殖或定型状态，并与这些细胞因子一起孵育，以评价细胞增殖、环氧合酶2（考克斯-2）表达、前列腺素（PG）和肌因子的释放以及生肌调节因子（MRF）的活化。我们发现，抑制IL-6受体可降低IL-1β和TNF-α诱导的细胞增殖，IL-1β的作用也涉及考克斯-2衍生的PG。这两种细胞因子都调节了肌细胞因子肌肉生长抑制素、鸢尾素、骨连接素和IL-15的释放。TNF-α和IL-6降低了增殖细胞中Pax 7的活性，并降低了增殖期和定型期MyoD和肌细胞生成素的活性。另外，IL-1β仅在定向细胞中增加肌细胞生成素活性。我们的数据揭示了IL-6和考克斯-2衍生的PG在IL-1β和TNF-α诱导的成肌细胞增殖中的关键作用，并支持TNF-α和IL-6与MRF激活之间的联系。我们得出结论，IL-1β和TNF-α在肌肉再生的初始阶段诱导类似的作用，但随着过程的进展，它们的作用之间存在关键差异，这为骨骼肌再生中的炎症信号传导带来了新的见解。
In this study, we investigated the effects and mechanisms of the pro-inflammatory cytokines IL-1β and TNF-α on the proliferation and commitment phases of myoblast differentiation. C2C12 mouse myoblast cells were cultured to reach a proliferated or committed status and were incubated with these cytokines for the evaluation of cell proliferation, cyclooxygenase 2 (COX-2) expression, release of prostaglandins (PGs) and myokines, and activation of myogenic regulatory factors (MRFs). We found that inhibition of the IL-6 receptor reduced IL-1β- and TNF-α-induced cell proliferation, and that the IL-1β effect also involved COX-2-derived PGs. Both cytokines modulated the release of the myokines myostatin, irisin, osteonectin, and IL-15. TNF-α and IL-6 reduced the activity of Pax7 in proliferated cells and reduced MyoD and myogenin activity at both proliferative and commitment stages. Otherwise, IL-1β increased myogenin activity only in committed cells. Our data reveal a key role of IL-6 and COX-2-derived PGs in IL-1β and TNF-α-induced myoblast proliferation and support the link between TNF-α and IL-6 and the activation of MRFs. We concluded that IL-1β and TNF-α induce similar effects at the initial stages of muscle regeneration but found critical differences between their effects with the progression of the process, bringing new insights into inflammatory signalling in skeletal muscle regeneration.
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影响因子：
5.5
作者：
Bondesen, BA;Mills, ST;Pavlath, GK
通讯作者：
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影响因子：
158.5
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10.1006/bbrc.2000.2682
发表时间：
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影响因子：
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通讯作者：
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