Interleukin-1beta stimulates early myogenesis of mouse C2C12 myoblasts: the impact on myogenic regulatory factors, extracellular matrix components, IGF binding proteins and protein kinases.

The purpose of the study was to examine the mechanisms important for early myogenesis in mouse C2C12 myogenic cells exposed to interleukin-1beta. Cyclin A and cyclin B1 were increased by interleukin-1beta (1 ng/ml), but the level of cyclin D1 and total DNA content was unaffected. Fusion index and the rate of protein synthesis was increased in the presence of IL-1beta, but these effects were limited to 3-day-treatment. IL-1beta increased the level of MyoD, myogenin and MHC on the 3rd day of differentiation, without altering the content of the active form of myostatin, as well as it augmented the level of fibronectin, integrin beta1 and full length 100 kDa form of ADAM12. IL-1beta caused a decrease in IGFBP-4 and IGFBP-6 levels and a marked increase in IGFBP-5. The phosphorylation of PKB and ERK1/2 and the cellular content of p38 were elevated by IL-1beta. We conclude that the myogenic effect of IL-1beta was limited to the onset of myoblast fusion and was associated with: i) increase in the level of myogenic transcription factors i.e. MyoD and myogenin expression, ii) modification of extracellular matrix assembly and signaling, manifested by an increase in fibronectin, integrin-beta1 and ADAM12 content, iii) drop in IGFBP-4 and IGFBP-6, and an increase in IGFBP-5, that could alter the local IGF-1 bioavailability, and iv) increase in phosphorylation of PKB and ERK1/2, and the expression of p38 kinase, leading to activation of intracellular pathways essential for myogenic differentiation.