Szalay K, Rázga Z, Duda E
Institute of Biochemistry, MTA Biological Research Center, Szeged/Hungary.
Eur J Cell Biol. 1997 Dec;74(4):391-8.
The presence of TNF and other inflammatory cytokines and their receptors is detected during embryonic development, but our knowledge about the role of these proteins in differentiation and development is very limited. TNF modulates the synthesis and activity of a number of transcriptional proteins that regulate the activity of tissue specific genes, therefore it may play a role in normal development. Since its synthesis is upregulated by stress and infections, it may also participate in the induction of pathological developmental processes and malformation. We investigated the effect of TNF in an in vitro differentiation system using C2 myoblasts. This inflammatory cytokine exerted a positive effect on the early steps of the process: it enhanced the proliferation and aggregation of myoblast cells. In contrast, TNF strongly inhibited the expression of those myogenic transcription factors (myoD and myogenin), which are known to be responsible for upregulated activity of muscle specific genes (like the genes of the myofilament proteins), and blocked the synthesis of mRNAs of myogenic differentiation markers (like skeletal alpha-actin, myosin heavy and light chains). As a result, these cells did not synthesize myofilament proteins and the organization of myofilaments did not take place in TNF-treated myoblasts.
在胚胎发育过程中可检测到肿瘤坏死因子（TNF）及其他炎性细胞因子及其受体，但我们对这些蛋白质在分化和发育中的作用了解非常有限。TNF可调节多种转录蛋白的合成与活性，而这些转录蛋白可调控组织特异性基因的活性，因此它可能在正常发育中发挥作用。由于其合成受应激和感染上调，它也可能参与病理性发育过程和畸形的诱导。我们使用C2成肌细胞在体外分化系统中研究了TNF的作用。这种炎性细胞因子对该过程的早期步骤产生了积极影响：它增强了成肌细胞的增殖和聚集。相反，TNF强烈抑制那些已知负责上调肌肉特异性基因（如肌丝蛋白基因）活性的肌源性转录因子（肌分化抗原和肌细胞生成素）的表达，并阻断肌源性分化标志物（如骨骼肌α-肌动蛋白、肌球蛋白重链和轻链）的mRNA合成。结果，这些细胞不合成肌丝蛋白，并且在经TNF处理的成肌细胞中未发生肌丝的组装。
