Activated Lymphocytes Secretome Inhibits Differentiation and Induces Proliferation of C2C12 Myoblasts

Background/Aims: ageing is associated with a marked decline in immune function which may contribute to the local environment that can influence the regenerative process of skeletal muscle cells. Methods: Herein, we focused on determining the effect of an activated immune system secretome on myoblast differentiation and proliferation as possible means to attenuate adverse effects of muscle aging. C2C12 myoblasts were used as model to assess the impact of lymphocyte conditioned media (CM) following anti-CD3/IL-2 activation. Results: Myoblasts cultured with activated lymphocytes CM exhibited reduced morphological and biochemical differentiation (98 +/- 20, p<0.005) and increased entry to the S Phase of the cell cycle (61% +/- 7, p<0.001), when compared with myoblasts cultured with non-activated lymphocytes CM. Associated with increased proliferation and reduced differentiation, muscle specific transcription factors MyoD and myogenin were significantly reduced in C2C12 treated with activated lymphocytes CM vs control CM, respectively (myoD: 0.5 +/- 0.12 fold reduction P<0.005); myogenin: 0.38 +/- 0.08 fold reduction; p<0.005). Moreover, key protein of proliferation pERK1/2 increased (46 +/- 11U/ml, p<0.05) whereas mediator of differentiation pAkt decreased (21 +/- 12U/ml, p<0.05) in C2C12 treated with activated vs. non-activated CM. Conclusion: our data demonstrate that, following activation, secretome of the immune system cells elicit marked regulatory effects on skeletal muscle growth and differentiation; enhancing the former with the loss of the latter. Copyright (C) 2014 S. Karger AG, Basel